Interactions by disorder – A matter of context
Open accessAbstract
Living organisms depend on timely and organized interactions between proteins linked in interactomes of high complexity. The recent increased precision by which protein interactions can be studied, and the enclosure of intrinsic structural disorder, suggest that it is time to zoom out and embrace protein interactions beyond the most central points of physical encounter. The present paper discusses protein-protein interactions in the view of structural disorder with an emphasis on flanking regions and contexts of disorder-based interactions. Context constitutes an overarching concept being of physicochemical, biomolecular, and physiological nature, but it also includes the immediate molecular context of the interaction. For intrinsically disordered proteins, which often function by exploiting short linear motifs, context contributes in highly regulatory and decisive manners and constitute a yet largely unrecognized source of interaction potential in a multitude of biological processes. Through selected examples, this review emphasizes how multivalency, charges and charge clusters, hydrophobic patches, dynamics, energetic frustration, and ensemble redistribution of flanking regions or disordered contexts are emerging as important contributors to allosteric regulation, positive and negative cooperativity, feedback regulation and negative selection in binding. The review emphasizes that understanding context, and in particular the role the molecular disordered context and flanking regions take on in protein interactions, constitute an untapped well of energetic modulation potential, also of relevance to drug discovery and development.
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Although there are clear context dependent modulations of intrinsic sequence-ensemble relationships, these modulations range from being negligible to predictable based on the sequence features of IDRs and the types of folded domains to which IDRs are tethered.
“Although there are clear context dependent modulations of intrinsic sequence-ensemble relationships, these modulations range from being negligible to predictable based on the sequence features of IDRs and the types of folded domains to which IDRs are tethered.80,81”
From AlphaFold and Implications for Intrinsically Disordered Proteins (2021) · cites this paper as [81]
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“However, this motif is part of a region with several hydrophobic patches, and GCN4 binds the Mediator co-activator component MED15 via multiple, low-affinity interactions, which additively contribute to activation activity (Drysdale et al., 1995; Warfield et al., 2014; Staller et al., 2018).”
BackgroundHelical Propensity in an Intrinsically Disordered Protein Accelerates Ligand Binding
Iešmantavičius, V., Dogan, J., Jemth, P., Teilum, K., & Kjærgaard, M. (2014) · Angewandte Chemie International Edition · doi:10.1002/anie.201307712 · Cited by 162 · see citing works
Hypersensitive termination of the hypoxic response by a disordered protein switch
Berlow, R. B., Dyson, H. J., & Wright, P. E. (2017) · Nature · doi:10.1038/nature21705 · Cited by 161 · cited 11× · see citing works
“The dynamics particularly of the N-terminal region of bound HIF-1 α was suggested to allow CITED2 to access a key surface on TAZ1, promoting ternary complex formation and eventually displacement of HIF-1 α .”
BackgroundMethodInfluentialContextual Specificity in Peptide-Mediated Protein Interactions
Stein, A., & Aloy, P. (2008) · PLoS ONE · doi:10.1371/journal.pone.0002524 · Cited by 160 · see citing works
Natively Unfolded Human Prothymosin α Adopts Partially Folded Collapsed Conformation at Acidic pH
Uversky, V. N., Gillespie, J. R., Millett, I. S., Khodyakova, A. V., Vasiliev, A. M., Chernovskaya, T. V., Vasilenko, R. N., Kozlovskaya, G. D., Dolgikh, D. A., Fink, A. L., et al. (1999) · Biochemistry · doi:10.1021/bi990752+ · Cited by 154 · cited 1× · see citing works
“Prothymosin-α (ProTα), a highly acidic, nuclear IDP, is expanded at neutral pH, but compacts as the pH decreases (Uversky et al., 1999).”
BackgroundDrysdale, C. M., Dueñas, E., Jackson, B. M., Reusser, U., Braus, G. H., & Hinnebusch, A. G. (1995) · Molecular and Cellular Biology · doi:10.1128/mcb.15.3.1220 · Cited by 154 · see citing works
The molecular mechanism of nuclear transport revealed by atomic-scale measurements
Hough, L. E., Dutta, K., Sparks, S., Temel, D. B., Kamal, A., Tetenbaum-Novatt, J. E., Rout, M. P., & Cowburn, D. (2015) · eLife · doi:10.7554/elife.10027 · Cited by 150 · cited 1× · see citing works
“…through, e.g., the specific expression of isoforms at different developmental stages that differ in their ability to interact with partners, as shown for the Ubx transcription factors (TFs), which are key players in Drosophila embryonic development (López et al., 1996; Hsiao et al., 2014).”
Sørensen, C. S., & Kjærgaard, M. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1904813116 · Cited by 145 · cited 1× · see citing works
“Interestingly, while hydrophobicity has been suggested to play a marginal role in IDR compaction (Marsh and Forman-kay, 2010), a correlation between the fraction and patterning of aromatic residues and chain compaction was recently established (Sørensen and Kjaergaard, 2019; Martin et al., 2020).”
BackgroundRTX Calcium Binding Motifs Are Intrinsically Disordered in the Absence of Calcium
Chenal, A., Guijarro, J. I., Raynal, B. D. E., Delepierre, M., & Ladant, D. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m807312200 · Cited by 144 · cited 1× · see citing works
“For the disordered region of the adenylate cyclase toxin (Chenal et al., 2009), Ca 2 + binding to > 40 repeats in toxin motifs (RTX) GGxGxDx[ (cid:127) , (cid:57) ] led to folding into a β -roll structure (Sotomayor Pérez et al., 2010) central to its secretion (O’Brien et al., 2018) ( Table 1 ).”
BackgroundStructural basis for pH-dependent retrieval of ER proteins from the Golgi by the KDEL receptor
Bräuer, P., Parker, J. L., Gerondopoulos, A., Zimmermann, I., Seeger, M. A., Barr, F. A., & Newstead, S. L. (2019) · Science · doi:10.1126/science.aaw2859 · Cited by 143 · see citing works
Describing sequence–ensemble relationships for intrinsically disordered proteins
Mao, A. H., Lyle, N., & Pappu, R. V. (2013) · Biochemical Journal · doi:10.1042/bj20121346 · Cited by 135 · cited 1× · see citing works
“To date, various studies have assessed the sequence-encoded conformational preferences of IDPs, using concepts from polymer physics reviewed in Mao et al. (2013) and by combining several biophysical techniques with molecular simulations.”
BackgroundEukaryotic transcription factors: paradigms of protein intrinsic disorder
Staby, L., O’Shea, C., Willemoës, M., Theisen, F. F., Kragelund, B. B., & Skriver, K. (2017) · Biochemical Journal · doi:10.1042/bcj20160631 · Cited by 134 · cited 2× · see citing works
“The activation activity of GCN4 depends on the SLiM 88W88LF (Table 1) (Warfield et al., 2014; Staby et al., 2017).”
BackgroundOpposing effects of Elk-1 multisite phosphorylation shape its response to ERK activation
Mylona, A., Theillet, F., Foster, C., Cheng, T. M. K., Miralles, F., Bates, P. A., Selenko, P., & Treisman, R. (2016) · Science · doi:10.1126/science.aad1872 · Cited by 133 · cited 1× · see citing works
“…have been observed, which may increase or decrease transient helicity in the vicinity of binding motifs, which in turn contributes to selection and deselection of binding partners as well as initiating degradation (Bah and Forman-Kay, 2016; Mylona et al., 2016; Hendus-Altenburger et al., 2017).”
BackgroundMutations in Disordered Regions Can Cause Disease by Creating Dileucine Motifs
Meyer, K., Kirchner, M., Uyar, B., Cheng, J.-Y., Russo, G., Hernandez-Miranda, L. R., Szymborska, A., Zauber, H., Rudolph, I.-M., Willnow, T. E., et al. (2018) · Cell · doi:10.1016/j.cell.2018.08.019 · Cited by 132 · see citing works
Intrinsic Disorder, Protein–Protein Interactions, and Disease
Uversky, V. N. (2017) · Advances in protein chemistry and structural biology · doi:10.1016/bs.apcsb.2017.06.005 · Cited by 118 · cited 2× · see citing works
“with an intrinsically disordered region (IDR), are key to network fidelity (Dosztányi et al., 2006; Oldfield et al., 2008; Staby et al., 2017; Uversky, 2018), and they exist in ensembles of almost isoenergetic states.”
BackgroundCryptic sequence features within the disordered protein p27 Kip1 regulate cell cycle signaling
Das, R. K., Huang, Y., Phillips, A. H., Kriwacki, R. W., & Pappu, R. V. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1516277113 · Cited by 117 · see citing works
Krystkowiak, I., & Davey, N. E. (2017) · Nucleic Acids Res. · doi:10.1093/nar/gkx238 · Cited by 116 · see citing works
The PCNA interaction motifs revisited: thinking outside the PIP-box
Prestel, A., Wichmann, N., Martins, J. M. D. S., Marabini, R., Kassem, N., Broendum, S. S., Otterlei, M., Nielsen, O., Willemoës, M., Ploug, M., et al. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03150-0 · Cited by 112 · cited 5× · see citing works
“PCNA has an enormous interactome (Moldovan et al., 2007; Prestel et al., 2019) and common to its binding partners is the Qxx8xx[FHT][FHY] PIP-box motif of which variations are known, including the PIP-degron for degradation QTD8xx[FHT][FHY]-X4-[KR] (Havens and Walter, 2009) (Table 1), and the APIM motif [KR]82[KR] fo…”
BackgroundInfluentialInteraction of the TAZ1 Domain of the CREB-Binding Protein with the Activation Domain of CITED2
Guzman, R. N. D., Martinez‐Yamout, M. A., Dyson, H. J., & Wright, P. E. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m310348200 · Cited by 108 · cited 1× · see citing works
“The two TFs use the core motif LP [ Q/E ] L for binding to the same site on TAZ1 ( Table 1 ), and bind with close to identical affinities (De Guzman et al., 2004; Berlow et al., 2017).”
BackgroundPredicting the targeting of tail-anchored proteins to subcellular compartments in mammalian cells
Costello, J. L., Castro, I. G., Camões, F., Schrader, T. A., McNeall, D., Yang, J., Giannopoulou, E., Gomes, S. R. A. M., Pogenberg, V., Bonekamp, N. A., et al. (2017) · Journal of Cell Science · doi:10.1242/jcs.200204 · Cited by 107 · cited 1× · see citing works
“Proteins with FFAT motifs (Loewen et al., 2003) communicate between the ER and other compartments by bridging (Murphy and Levine, 2016; Costello et al., 2017; Slee and Levine, 2019).”
BackgroundAffinity and specificity of motif-based protein–protein interactions
Ivarsson, Y., & Jemth, P. (2018) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2018.09.009 · Cited by 107 · cited 1× · see citing works
“The SLiM is the central anchoring site for many IDP interactions and a recent review discusses the molecular details of SLiM-based affinity and specificity (Ivarsson and Jemth, 2019).”
BackgroundComputational identification of MoRFs in protein sequences
Malhis, N., & Gsponer, J. A. (2015) · Bioinformatics · doi:10.1093/bioinformatics/btv060 · Cited by 101 · see citing works
Parkinson's Disease-associated α-Synuclein Is a Calmodulin Substrate
Martinez, J., Moeller, I., Erdjument‐Bromage, H., Tempst, P., & Lauring, B. P. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m209020200 · Cited by 100 · cited 1× · see citing works
“For aSN, this meant that sub-states of the aggregation-prone region were relieved of negative coupling, which the authors suggested may explain how calmodulin facilitates aggregation of aSN (Martinez et al., 2003).”
BackgroundOrganellar Na+/H+ Exchangers: Novel Players in Organelle pH Regulation and Their Emerging Functions
Ohgaki, R., van IJzendoorn, S. C. D., Matsushita, M., Hoekstra, D., & Kanazawa, H. (2010) · Biochemistry · doi:10.1021/bi101082e · Cited by 98 · cited 1× · see citing works
“…are brain specific, e.g., NHE6 and NHE9 (Schwede et al., 2014; Zhao et al., 2016), and some are ubiquitously located in the plasma membrane, such as NHE1, while other isoforms are localized in specific organellar membranes (Ohgaki et al., 2011; Prasad and Rao, 2015; Pedersen and Counillon, 2019).”
BackgroundLi, J., White, J. T., Saavedra, H. G., Wrabl, J. O., Motlagh, H. N., Liu, K., Sowers, J. R., Schroer, T. A., Thompson, E. B., & Hilser, V. J. (2017) · eLife · doi:10.7554/elife.30688 · Cited by 98 · cited 2× · see citing works
“The importance of such energetic frustration in IDP interactions has also been demonstrated from work on the glucocorticoid receptor (GR), where the disordered domain allosterically controls function by principles of energetic frustration (Li et al., 2018).”
BackgroundWarfield, L., Tuttle, L. M., Pacheco, D., Klevit, R. E., & Hahn, S. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1412088111 · Cited by 94 · cited 2× · see citing works
“The activation activity of GCN4 depends on the SLiM W LF ( Table 1 ) (Warfield et al., 2014; Staby et al., 2017).”
BackgroundMethodFuruita, K., Jee, J., Fukada, H., Mishima, M., & Kojima, C. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.082602 · Cited by 91 · cited 2× · see citing works
“The core of the FFAT motif, EFFDAxE, found in, e.g., oxysterol-binding protein (OSBP) (Furuita et al., 2010), is an extended region of seven residues ( Table 1 ), the second and fifth of which bind into pockets in the integral ER membrane protein VAMP-associated protein (VAP) (Kaiser et al., 2005).”
BackgroundMolecular Recognition by Templated Folding of an Intrinsically Disordered Protein
Toto, A., Camilloni, C., Giri, R., Brunori, M., Vendruscolo, M., & Gianni, S. (2016) · Scientific Reports · doi:10.1038/srep21994 · Cited by 90 · cited 1× · see citing works
“Conformational heterogeneity, characteristic of many ID-based interactions (Fuxreiter, 2019), is also regulated by residues outside the SLiM-binding site, where they form transient heterogeneous contacts, which may facilitate partner-templated coupled folding and binding (Toto et al., 2016).”
BackgroundUnderstanding Pre-Structured Motifs (PreSMos) in Intrinsically Unfolded Proteins
Lee, S., Kim, D.-H., Han, J. J., Cha, E., Lim, J., Cho, Y., Lee, C., & Han, K. (2012) · Current Protein and Peptide Science · doi:10.2174/138920312799277974 · Cited by 88 · cited 1× · see citing works
“, 2018) or pre-structured motifs (PreSMos) (Lee et al., 2012), the flanking regions can modulate the structural context of the motif and hence interactions.”
BackgroundUyar, B., Weatheritt, R. J., Dinkel, H., Davey, N. E., & Gibson, T. J. (2014) · Molecular BioSystems · doi:10.1039/c4mb00290c · Cited by 87 · cited 2× · see citing works
“A proteome-wide study found that 22% of all human disease mutations locate to disordered regions (Uyar et al., 2014).”
BackgroundEmerging roles of Na+/H+ exchangers in epilepsy and developmental brain disorders
Zhao, H., Carney, K. E., Falgoust, L., Pan, J. W., Sun, D., & Zhang, Z. (2016) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2016.02.002 · Cited by 87 · see citing works
Zheleva, D. I., Zhelev, N., Fischer, P. M., Duff, S. V., Warbrick, E., Blake, D., & Lane, D. P. (2000) · Biochemistry · doi:10.1021/bi992498r · Cited by 86 · see citing works
Jones, R. E., Wegrzyn, R. J., Patrick, D. R., Balishin, N. L., Vuocolo, G. A., Riemen, M. W., Defeo-Jones, D., Garsky, V. M., Heimbrook, D. C., & Oliff, A. I. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)38226-2 · Cited by 82 · see citing works
Long-Range Correlated Dynamics in Intrinsically Disordered Proteins
Parigi, G., Rezaei‐Ghaleh, N., Giachetti, A., Becker, S., Fernández, C. O., Blackledge, M. J., Griesinger, C., Zweckstetter, M., & Luchinat, C. (2014) · Journal of the American Chemical Society · doi:10.1021/ja506820r · Cited by 80 · cited 2× · see citing works
“Using FFC relaxometry, it was shown for four IDPs that slow reorientations on the several nanosecond time scale occurred in the chain, without specific residue interactions, but rather based on frictionmediated coupling (Parigi et al., 2014).”
MethodConformational Prerequisites for Formation of Amyloid Fibrils from Histones
Munishkina, L. A., Fink, A. L., & Uversky, V. N. (2004) · Journal of Molecular Biology · doi:10.1016/j.jmb.2004.06.094 · Cited by 77 · cited 1× · see citing works
“Similarly, proteins with high overall positive charge, such as core histones, partially fold when pH increases, affecting DNA binding (Hansen et al., 1998; Munishkina et al., 2004).”
BackgroundFold or not to fold upon binding — does it really matter?
Fuxreiter, M. (2018) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2018.09.008 · Cited by 76 · see citing works
A Slow Conformational Switch in the BMAL1 Transactivation Domain Modulates Circadian Rhythms
Gustafson, C. L., Parsley, N. C., Asimgil, H., Lee, H., Ahlbach, C., Michael, A. K., Xu, H., Williams, O. L., Davis, T. L., Liu, A. C., et al. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.04.011 · Cited by 75 · cited 2× · see citing works
“Locking the switch into the trans conformation results in a shorter circadian period compared to the wild-type, while inhibiting cyclophilins, which accelerate the interconversion between isomers, lengthens the circadian period in a dose-dependent manner (Gustafson et al., 2017).”
BackgroundPolymer effects modulate binding affinities in disordered proteins
Vancraenenbroeck, R., Harel, Y. S., Zheng, W., & Hofmann, H. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1904997116 · Cited by 75 · cited 1× · see citing works
“However, ions not only affect structure and conformational properties via distinct binding, but their presence can also lead to changes in the ensemble, as shown for five different IDPs, which all expanded due to an increase in salt concentration (Vancraenenbroeck et al., 2019).”
BackgroundWicky, B., Shammas, S. L., & Clarke, J. (2017) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.1705105114 · Cited by 73 · cited 1× · see citing works
“Salts also tune disorder-based affinities and binding kinetics, as demonstrated for two different IDPs (Wicky et al., 2017), where the observed effects were dependent on the specific ions and not simply correlated to the ionic strength.”
BackgroundPrasad, H., & Rao, R. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.602219 · Cited by 72 · cited 1× · see citing works
“, 2016), and some are ubiquitously located in the plasma membrane, such as NHE1, while other isoforms are localized in specific organellar membranes (Ohgaki et al., 2011; Prasad and Rao, 2015; Pedersen and Counillon, 2019).”
BackgroundStructural Dynamics and Regulation of the Mammalian SLC9A Family of Na+/H+ Exchangers
Hendus-Altenburger, R., Kragelund, B. B., & Pedersen, S. F. (2014) · Current topics in membranes · doi:10.1016/b978-0-12-800223-0.00002-5 · Cited by 72 · cited 1× · see citing works
“…and the nine isoforms have similar membrane transport functions, but have IDRs of different lengths with varying SLiM content and sequence (Nørholm et al., 2011; Hendus-Altenburger et al., 2014), suggesting that the mechanisms and regulations underlying their function in the membrane, differ.”
BackgroundMapping, modeling, and characterization of protein–protein interactions on a proteomic scale
Cafarelli, T. M., Desbuleux, A., Wang, Y., Choi, S. G., Ridder, D. D., & Vidal, M. (2017) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2017.05.003 · Cited by 72 · see citing works
Rapali, P., Radnai, L., Süveges, D., Harmat, V., Tölgyesi, F., Wahlgren, W. Y., Katona, G., Nyitray, L., & Pál, G. (2011) · PLoS ONE · doi:10.1371/journal.pone.0018818 · Cited by 71 · see citing works
Sotomayor-Pérez, A.-C., Karst, J. C., Davi, M., Guijarro, J. I., Ladant, D., & Chenal, A. (2010) · Journal of Molecular Biology · doi:10.1016/j.jmb.2010.01.031 · Cited by 68 · see citing works
Conformation of bovine myelin basic protein purified with bound lipids
Polverini, E., Fasano, A., Zito, F. A., Riccio, P., & CAVATORTA, P. (1999) · European Biophysics Journal · doi:10.1007/s002490050218 · Cited by 66 · cited 1× · see citing works
“MBP is disordered, but folds into an α -helical structure upon electrostatic interaction with the membrane (Polverini et al., 1999; Harauz et al., 2009), a transition highly regulated by salt and Ca 2 + (Raasakka et al., 2019).”
BackgroundO’Shea, C., Staby, L., Bendsen, S. K., Tidemand, F. G., Redsted, A., Willemoës, M., Kragelund, B. B., & Skriver, K. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.753426 · Cited by 65 · see citing works
Genes for endosomal NHE6 and NHE9 are misregulated in autism brains
Schwede, M., Garbett, K. A., Mirnics, K., Geschwind, D. H., & Morrow, E. M. (2013) · Molecular Psychiatry · doi:10.1038/mp.2013.28 · Cited by 61 · see citing works
Nørholm, A., Hendus-Altenburger, R., Bjerre, G., Kjærgaard, M., Pedersen, S. F., & Kragelund, B. B. (2011) · Biochemistry · doi:10.1021/bi1019989 · Cited by 61 · see citing works
Yi, S., Boys, B. L., Brickenden, A. M., Konermann, L., & Choy, W. (2007) · Biochemistry · doi:10.1021/bi7014822 · Cited by 59 · see citing works
Structural insights into the function of ZRANB3 in replication stress response
Šebesta, M., Cooper, C. D. O., Ariza, A., Carnie, C. J., & Ahel, D. (2017) · Nature Communications · doi:10.1038/ncomms15847 · Cited by 58 · see citing works
Sharma, R., Bayarjargal, M., Tsunoda, T., Patil, A., & Sharma, A. K. (2017) · Journal of Theoretical Biology · doi:10.1016/j.jtbi.2017.10.015 · Cited by 55 · cited 1× · see citing works
“Finally, when SLiMs are placed in pre-structured contexts, defined as molecular recognition features (MoRFs) (Malhis and Gsponer, 2015; Sharma et al., 2018) or pre-structured motifs (PreSMos) (Lee et al., 2012), the flanking regions can modulate the structural context of the motif and hence…”
BackgroundMultivalency regulates activity in an intrinsically disordered transcription factor
Clark, S. J., Myers, J. B., King, A., Fiala, R., Nováček, J., Pearce, F. G., Heierhorst, J., Reichow, S., & Barbar, E. J. (2018) · eLife · doi:10.7554/elife.36258 · Cited by 55 · see citing works
The solvent side of proteinaceous membrane-less organelles in light of aqueous two-phase systems
Zaslavsky, B. Y., Ferreira, L. A., Darling, A. L., & Uversky, V. N. (2018) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2018.06.030 · Cited by 55 · see citing works
Slee, J. A., & Levine, T. P. (2019) · Contact · doi:10.1177/2515256419883136 · Cited by 54 · cited 1× · see citing works
“Proteins with FFAT motifs (Loewen et al., 2003) communicate between the ER and other compartments by bridging (Murphy and Levine, 2016; Costello et al., 2017; Slee and Levine, 2019).”
BackgroundRandom coil chemical shifts for serine, threonine and tyrosine phosphorylation over a broad pH range
Hendus-Altenburger, R., Fernandes, C. B., Bugge, K., Kunze, M. B. A., Boomsma, W., & Kragelund, B. B. (2019) · Journal of Biomolecular NMR · doi:10.1007/s10858-019-00283-z · Cited by 50 · see citing works
Li, J., Motlagh, H. N., Chakuroff, C., Thompson, E. B., & Hilser, V. J. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.355651 · Cited by 49 · cited 1× · see citing works
“For GR, signaling is tuned by changing the length of the intrinsically disordered context through translational isoforms, resulting in modulation of the degree of energetic frustration (Li et al., 2012, 2018).”
BackgroundElucidation of the binding preferences of peptide recognition modules: SH3 and PDZ domains
Teyra, J., Sidhu, S. S., & Kim, P. M. (2012) · FEBS Letters · doi:10.1016/j.febslet.2012.05.043 · Cited by 49 · see citing works
Majava, V., Petoukhov, M. V., Hayashi, N., Pirilä, P., Svergun, D. I., & Kursula, P. (2008) · BMC Structural Biology · doi:10.1186/1472-6807-8-10 · Cited by 46 · cited 1× · see citing works
“Another example is the highly positively charged myelin basic protein (MBP), essential for the formation and stability of the myelin sheath in the central nervous system (Majava et al., 2008; De Avila et al., 2014).”
BackgroundXiang, W., Menges, S., Schlachetzki, J. C. M., Meixner, H., Hoffmann, A.-C., Schlötzer-Schrehardt, U. M., Becker, C., Winkler, J., & Klucken, J. (2015) · Molecular Neurodegeneration · doi:10.1186/s13024-015-0004-0 · Cited by 44 · cited 1× · see citing works
“Some disease-related mutations are SLiM-conserving, leaving affinity unperturbed, but with mutations located in the context resulting in altered specificity, cross-reactivity, and self-association as in the case of some neurodegenerative diseases (Uyar et al., 2014; Xiang et al., 2015).”
BackgroundHendus-Altenburger, R., Lambrughi, M., Terkelsen, T., Pedersen, S. F., Papaleo, E., Lindorff‐Larsen, K., & Kragelund, B. B. (2017) · Cellular Signalling · doi:10.1016/j.cellsig.2017.05.015 · Cited by 44 · see citing works
Avidity within the N‐terminal anchor drives α‐synuclein membrane interaction and insertion
Cholak, E., Bugge, K., Khondker, A., Gauger, K., Pedraz‐Cuesta, E., Pedersen, M. E., Bucciarelli, S., Vestergaard, B., Pedersen, S. F., Rheinstadter, M. C., et al. (2020) · The FASEB Journal · doi:10.1096/fj.202000107r · Cited by 44 · see citing works
Evolution of domain–peptide interactions to coadapt specificity and affinity to functional diversity
Kelil, A., Levy, E. D., & Michnick, S. W. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1518469113 · Cited by 43 · see citing works
Berlow, R. B., Martinez‐Yamout, M. A., Dyson, H. J., & Wright, P. E. (2019) · Biochemistry · doi:10.1021/acs.biochem.8b01290 · Cited by 43 · see citing works
Multivalency regulates activity in an intrinsically disordered transcription factor
Clark, S. J., Myers, J. B., King, A., et al. (2018) · eLife · doi:10.7554/elife.40684 · Cited by 43 · cited 6× · see citing works
“Cooperativity driven by flanking regions is elegantly demonstrated by the IDRs constituting the activation domain of the zinc finger TF ataxia telangiectasia mutated substrate Chk2-interacting Zn 2 + -finger protein (ASCIZ) (Clark et al., 2018).”
BackgroundInfluentialMultivalent IDP assemblies: Unique properties of LC8‐associated, IDP duplex scaffolds
Clark, S. A., Jespersen, N. E., Woodward, C. K., & Barbar, E. J. (2015) · FEBS Letters · doi:10.1016/j.febslet.2015.07.032 · Cited by 41 · see citing works
Palópoli, N., Foutel, N. S. G., Gibson, T. J., & Chemes, L. B. (2018) · Protein Engineering Design and Selection · doi:10.1093/protein/gzx068 · Cited by 40 · cited 3× · see citing works
“Here, negative charges in the flanking regions act as affinity and specificity modulators (Figure 1B) (Palopoli et al., 2018), conversely regulated by introduction of negative charge from phosphorylation of binding regions on the Rbs (Knudsen and Wang, 1996).”
BackgroundD-cycloserine uses an active transport mechanism in the human intestinal cell line Caco 2
Ranaldi, G., Islam, K., & Sambuy, Y. (1994) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.38.6.1239 · Cited by 39 · cited 5× · see citing works
“The multivalency of ASCIZ and Chia allows both positive and negative cooperativity in its interaction with LC8.”
BackgroundInfluentialBeyond KDEL: The Role of Positions 5 and 6 in Determining ER Localization
Alanen, H. I., Raykhel, I. B., Luukas, M. J., Salo, K. E. H., & Ruddock, L. W. (2011) · Journal of Molecular Biology · doi:10.1016/j.jmb.2011.03.070 · Cited by 35 · cited 2× · see citing works
“However, the flanking regions may also have a highly hydrophobic character, as for the flanks of the [HKR]DEL SLiM (Alanen et al., 2011).”
BackgroundBugge, K., Staby, L., Kemplen, K. R., O’Shea, C., Bendsen, S. K., Jensen, M. K., Olsen, J. G., Skriver, K., & Kragelund, B. B. (2018) · Structure · doi:10.1016/j.str.2018.03.013 · Cited by 35 · cited 2× · see citing works
“For the plant TFs dehydration response element binding proteins 2A (DREB2A) and ANAC013, which both use the SLiM for binding to the cellular hub protein Radical Induced Cell Death1 (Bugge et al., 2018), disordered regions surrounding the binding motif exert positive and negative allosteric effects on binding, respectiv…”
BackgroundCragnell, C., Staby, L., Lenton, S., Kragelund, B. B., & Skepö, M. (2019) · Biomolecules · doi:10.3390/biom9050168 · Cited by 35 · cited 2× · see citing works
“Chain compaction may further be affected by metal ions, as observed for Zn 2 + binding to ProT α , and to histatin, a small peptide of the mouth, here promoting formation of higher order structures (Cragnell et al., 2019).”
BackgroundLee, C., Kalmár, L., Xue, B., Tompa, P., Daughdrill, G. W., Uversky, V. N., & Han, K. (2013) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2013.10.042 · Cited by 34 · cited 1× · see citing works
“, been shown that when a proline was mutated in an N-terminal flanking region, helicity was significantly decreased, whereas when mutated in the C-terminal flanking region, the helical content increased (Lee et al., 2014).”
BackgroundThe Anchored Flexibility Model in LC8 Motif Recognition: Insights from the Chica Complex
Clark, S. A., Nyarko, A., Löhr, F., Karplus, P. A., & Barbar, E. J. (2015) · Biochemistry · doi:10.1021/acs.biochem.5b01099 · Cited by 31 · see citing works
Kurzbach, D., Vanas, A., Flamm, A. G., Tarnoczi, N., Kontaxis, G., Maltar‐Strmečki, N., Widder, K., Hinderberger, D., & Konrat, R. (2015) · Physical Chemistry Chemical Physics · doi:10.1039/c5cp04858c · Cited by 30 · see citing works
Mei, M., Zhai, C., Li, X., Zhou, Y., Peng, W., Ma, L., Wang, Q., Iverson, B. L., Zhang, G., & Li, Y. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m117.812107 · Cited by 30 · see citing works
O'Brien, D. P., Pérez, A. C. S., Karst, J. C., Cannella, S. E., Enguéné, V. Y. N., Hessel, A., Raoux‐Barbot, D., Voegele, A., Subrini, O., Davi, M., et al. (2018) · Toxicon · doi:10.1016/j.toxicon.2018.01.007 · Cited by 26 · see citing works
Christensen, L. F., Staby, L., Bugge, K., O’Shea, C., Kragelund, B. B., & Skriver, K. (2019) · Scientific Reports · doi:10.1038/s41598-019-55385-3 · Cited by 26 · see citing works
Intrinsically Disordered Proteins
Kragelund, B. B., & Skriver, K. (2020) · Methods in molecular biology · doi:10.1007/978-1-0716-0524-0 · Cited by 25 · see citing works
Beier, A., Schwarz, T. C., Kurzbach, D., Platzer, G., Tribuzio, F., & Konrat, R. (2018) · Journal of Molecular Biology · doi:10.1016/j.jmb.2018.04.035 · Cited by 25 · cited 3× · see citing works
“Both proteins exhibited both correlated, anti-correlated and uncorrelated long-range chain fluctuations (Beier et al., 2018), with two residues being correlated if they display concerted motions or undergo simultaneous transitions between different conformational states, anti-correlated if they have…”
BackgroundMethodInfluentialKurzbach, D., Beier, A., Vanas, A., Flamm, A. G., Platzer, G., Schwarz, T. C., & Konrat, R. (2017) · Physical Chemistry Chemical Physics · doi:10.1039/c7cp00430c · Cited by 24 · cited 1× · see citing works
“Providing further details, a method based on PRE NMR, termed paramagnetic relaxation interference (PRI), allowed detection of correlated motions through covariance analysis of the effect of adding two paramagnetic labels to the same chain (Kurzbach et al., 2016, 2017).”
MethodHsiao, H., Gonzalez, K. L., Catanese, D. J., Jordy, K. E., Matthews, K. S., & Bondos, S. E. (2014) · PLoS ONE · doi:10.1371/journal.pone.0108217 · Cited by 21 · see citing works
Mapping multivalency in the CLIP-170–EB1 microtubule plus-end complex
Chen, Y., Wang, P., & Slep, K. C. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.006125 · Cited by 21 · see citing works
Noval, M. G., Gallo, M. L., Perrone, S., Salvay, A. G., Chemes, L. B., & Gay, G. D. P. (2013) · PLoS ONE · doi:10.1371/journal.pone.0072760 · Cited by 20 · cited 1× · see citing works
“A similar effect was seen for pocket proteins of the retinoblastoma protein (Rb) family, that bind the SLiM LxCxE, present in host and viral interactors of the Rb family (Jones et al., 1990; Noval et al., 2013).”
BackgroundSharma, A. K., Dehzangi, A., Lyons, J., Imoto, S., Miyano, S., Nakai, K., & Patil, A. (2014) · PLoS ONE · doi:10.1371/journal.pone.0089890 · Cited by 20 · cited 2× · see citing works
“For many IDPs, their interactions – and hence their contacts to their partner molecule – are made via short, sequence-embedded motifs of limited information (Sharma et al., 2014; Davey et al., 2015).”
BackgroundGorelik, M., & Davidson, A. R. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.330753 · Cited by 20 · see citing works
Raasakka, A., Jones, N. C., Hoffmann, S. V., & Kursula, P. (2019) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2019.02.025 · Cited by 19 · cited 1× · see citing works
“, 2009), a transition highly regulated by salt and Ca2+ (Raasakka et al., 2019).”
BackgroundAllovalency revisited: An analysis of multisite phosphorylation and substrate rebinding
Locasale, J. W. (2008) · The Journal of Chemical Physics · doi:10.1063/1.2841124 · Cited by 18 · cited 2× · see citing works
“The binding is cooperative, with almost no detectable binding until a sixth arbitrary site among ten becomes phosphorylated, producing strong binding (Mittag et al., 2008); a scenario only possible in the context of a flexible, dynamic chain (Locasale, 2008).”
BackgroundL�pez, A. J., Artero, R. D., & P�rez-Alonso, M. (1996) · Development Genes and Evolution · doi:10.1007/bf00377226 · Cited by 17 · see citing works
Avila, M. D., Vassall, K. A., Smith, G. S. T., Bamm, V. V., & Harauz, G. (2014) · Bioscience Reports · doi:10.1042/bsr20140149 · Cited by 16 · see citing works
Stender, E. G. P., O’Shea, C., & Skriver, K. (2015) · Plant Signaling & Behavior · doi:10.1080/15592324.2015.1010967 · Cited by 15 · cited 1× · see citing works
“, 2017) (Figure 1G and Table 1), possibly reflected in the function-related conservation of the disorder-order profiles for the NAC transcription factors (Stender et al., 2015).”
BackgroundGarg, A., Orrù, R., Ye, W., Distler, U., Chojnacki, J. E., Köhn, M., Tenzer, S., Sönnichsen, C., & Wolf, E. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.ra119.009845 · Cited by 15 · see citing works
Organizing Junctions at the Cell-Cell Interface
Akhmanova, A. S., & Yap, A. S. (2008) · Cell · doi:10.1016/j.cell.2008.11.002 · Cited by 12 · see citing works
Evolution of the activation domain in a Hox transcription factor
Liu, Y., Huang, A., Booth, R. M., Mendes, G. G., Merchant, Z., Matthews, K. S., & Bondos, S. E. (2018) · The International Journal of Developmental Biology · doi:10.1387/ijdb.180151sb · Cited by 6 · cited 1× · see citing works
“, 2002) revealed that the strength of the activation domains changed during evolution, and that the location of the activation domain moved relative to conserved motifs and sub-domain organization (Liu et al., 2018).”
BackgroundCorrection to: Intrinsically Disordered Proteins
Kragelund, B. B., & Skriver, K. (2021) · Methods in molecular biology · doi:10.1007/978-1-0716-0524-0_47 · Cited by 4 · see citing works
Li, J., White, J. T., Saavedra, H. G., Wrabl, J. O., Motlagh, H. N., Liu, K., Sowers, J. R., Schroer, T. A., Thompson, E. B., & Hilser, V. J. (2018) · eLife · doi:10.7554/elife.35768 · Cited by 2 · cited 2× · see citing works
“The importance of such energetic frustration in IDP interactions has also been demonstrated from work on the glucocorticoid receptor (GR), where the disordered domain allosterically controls function by principles of energetic frustration (Li et al., 2018).”
BackgroundRichardson, M. (1999) · doi:10.1002/(sici)1521-1878(199907)21:7
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The molecular basis for cellular function of intrinsically disordered protein regions
Holehouse, A. S., & Kragelund, B. B. (2023) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-023-00673-0 · Cited by 717 · see citing works
“…presence of osmolytes or ions; (ii) the chemical context of the IDR, namely, PTMs and changes in pH leading to protonation and deprotonation effects 41 ; and (iii) the structural context, that is, the presence or absence Intrinsically disordered regions (IDRs) have critical cellular roles across…”
AlphaFold and Implications for Intrinsically Disordered Proteins
Ruff, K. M., & Pappu, R. V. (2021) · Journal of Molecular Biology · doi:10.1016/j.jmb.2021.167208 · Cited by 635 · see citing works
Abyzov, A., Blackledge, M., & Zweckstetter, M. (2022) · Chemical Reviews · doi:10.1021/acs.chemrev.1c00774 · Cited by 215 · see citing works
Brocca, S., Grandori, R., Longhi, S., & Uversky, V. N. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21239045 · Cited by 189 · see citing works
ELM—the Eukaryotic Linear Motif resource—2024 update
Kumar, M., Michael, S., Alvarado-Valverde, J., Zeke, A., Lázár, T., Glavina, J., Nagy‐Kanta, E., Donagh, J. M., Kálmán, Z. E., Pascarelli, S., et al. (2023) · Nucleic Acids Research · doi:10.1093/nar/gkad1058 · Cited by 185 · see citing works
“SLiMs bind partner protein domains with moderate affinity and therefore in many contexts they exhibit co-operativity to achieve their functional output ( 22–24 ).”
BackgroundCamacho‐Zarco, A. R., Schnapka, V., Guseva, S., Abyzov, A., Adamski, W., Milles, S., Jensen, M. R., Žı́dek, L., Salvi, N., & Blackledge, M. J. (2022) · Chemical Reviews · doi:10.1021/acs.chemrev.1c01023 · Cited by 148 · see citing works
PED in 2021: a major update of the protein ensemble database for intrinsically disordered proteins
Lazar, T., Martínez-Pérez, E., Quaglia, F., Hatos, A., Chemes, L. B., Iserte, J. A., Méndez, N. A., Garrone, N. A., Saldaño, T. E., Marchetti, J., et al. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkaa1021 · Cited by 142 · see citing works
“However, this recent abundance of LDRs is predominantly due to the context-dependent folding of proteins with conditional disorder, such as pH sensitivity, PTM-dependent folding, localization-dependent disorder and folding upon binding to a partner (7–9).”
BackgroundBinding Revisited—Avidity in Cellular Function and Signaling
Erlendsson, S., & Teilum, K. (2021) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2020.615565 · Cited by 109 · see citing works
“…has also been expanded to include interactions involving fully flexible systems such as intrinsically disordered proteins (IDPs), and systems with less specific binding sequences e.g., phosphorylation sites or short linear motifs (SLiMs) (Mittag et al., 2008; Tompa, 2014; Bugge et al., 2020).”
BackgroundSystematic discovery of protein interaction interfaces using AlphaFold and experimental validation
Lee, C. Y., Hubrich, D., Varga, J. K., Schäfer, C., Welzel, M., Schumbera, E., Djokic, M., Strom, J. M., Schönfeld, J., Geist, J. L., et al. (2024) · Molecular Systems Biology · doi:10.1038/s44320-023-00005-6 · Cited by 105 · see citing works
“Various studies have highlighted that fl anking sequences of motifs can in fl uence binding af fi nities and speci fi cities (Luck et al, 2012; Bugge et al, 2020).”
Systematic discovery of protein interaction interfaces using AlphaFold and experimental validation
Lee, C. Y., Hubrich, D., Varga, J. K., Schäfer, C., Welzel, M., Schumbera, E., Đokić, M., Strom, J. M., Schönfeld, J., Geist, J. L., et al. (2023) · doi:10.1101/2023.08.07.552219 · Cited by 105 · see citing works
Molecular determinants of condensate composition
Holehouse, A. S., & Alberti, S. (2025) · Molecular Cell · doi:10.1016/j.molcel.2024.12.021 · Cited by 102 · see citing works
Sequence-based prediction of intermolecular interactions driven by disordered regions
Ginell, G. M., Emenecker, R. J., Lotthammer, J. M., Keeley, A. T., Plassmeyer, S. P., Razo, N. J., Usher, E. T., Pelham, J. F., & Holehouse, A. S. (2025) · Science · doi:10.1126/science.adq8381 · Cited by 102 · see citing works
Intrinsically disordered proteins: modes of binding with emphasis on disordered domains
Morris, O. M., Torpey, J. H., & Isaacson, R. L. (2021) · Open Biology · doi:10.1098/rsob.210222 · Cited by 99 · see citing works
“It has been widely reported that flanking regions modulate the nature of the interaction between an IDP and its target, contributing to binding affinity and specificity [40].”
BackgroundInfluentialIntrinsically disordered proteins/regions and insight into their biomolecular interactions
Chakrabarti, P., & Chakravarty, D. (2022) · Biophysical Chemistry · doi:10.1016/j.bpc.2022.106769 · Cited by 90 · see citing works
Interaction modules that impart specificity to disordered protein
Čermáková, K., & Hodges, H. C. (2023) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2023.01.004 · Cited by 92 · see citing works
Intrinsically Disordered Proteins: Critical Components of the Wetware
Kulkarni, P., Bhattacharya, S., Achuthan, S., Behal, A., Jolly, M. K., Kotnala, S., Mohanty, A. R., Rangarajan, G., Salgia, R., & Uversky, V. N. (2022) · Chemical Reviews · doi:10.1021/acs.chemrev.1c00848 · Cited by 87 · see citing works
Lindorff-Larsen, K., & Kragelund, B. B. (2021) · Journal of Molecular Biology · doi:10.1016/j.jmb.2021.167196 · Cited by 85 · see citing works
Self-citationProteome‐scale mapping of binding sites in the unstructured regions of the human proteome
Benz, C., Ali, M., Krystkowiak, I., Simonetti, L., Sayadi, A., Mihalič, F., Kliche, J., Andersson, E., Jemth, P., Davey, N. E., et al. (2022) · Molecular Systems Biology · doi:10.15252/msb.202110584 · Cited by 79 · see citing works
“Many SLiM-based PPIs rely on additional binding sites present in the interacting proteins, which further complicates their identification (Ivarsson & Jemth, 2019; Bugge et al , 2020).”
Theillet, F., & Luchinat, E. (2022) · Progress in Nuclear Magnetic Resonance Spectroscopy · doi:10.1016/j.pnmrs.2022.04.002 · Cited by 82 · see citing works
Zeng, X., Ruff, K. M., & Pappu, R. V. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2200559119 · Cited by 71 · see citing works
“Such transitions, especially in the context of tethered systems, are likely to make important contributions to the spatial and temporal control over biochemical reactions where IDRs modulate the effective concentrations of ligands around binding sites or of substrates around active sites of enzymes (31, 32, 34, 56, 84…”
BackgroundOn the specificity of protein–protein interactions in the context of disorder
Teilum, K., Olsen, J. G., & Kragelund, B. B. (2021) · Biochemical Journal · doi:10.1042/bcj20200828 · Cited by 72 · see citing works
Expanding the molecular grammar of polar residues and arginine in FUS phase separation
Wake, N., Weng, S.-L., Zheng, T., Wang, S., Kirilenko, V., Mittal, J., & Fawzi, N. L. (2025) · Nature Chemical Biology · doi:10.1038/s41589-024-01828-6 · Cited by 66 · see citing works
“Alternatively, considering the role of various residue pair contacts in PS, one could adopt a nonbinary inclusive classification where most (if not all) residues contribute to PS depending on the context and other environmental factors such as temperature, salt and pH 57,58 .”
Intrinsically disordered regions as facilitators of the transcription factor target search
Jonas, F., Navon, Y., & Barkai, N. (2025) · Nature Reviews Genetics · doi:10.1038/s41576-025-00816-3 · Cited by 63 · see citing works
“However, functionally conserved IDRs show little sequence conservation when tested using alignment-based comparative tools, suggesting distinct sequence–function relationships that are independent of linear residue ordering 36–42 .”
Naudi-Fabra, S., Tengo, M., Jensen, M. R., Blackledge, M. J., & Milles, S. (2021) · Journal of the American Chemical Society · doi:10.1021/jacs.1c06264 · Cited by 62 · see citing works
actifpTM: a refined confidence metric of AlphaFold2 predictions involving flexible regions
Varga, J. K., Ovchinnikov, S., & Schueler‐Furman, O. (2025) · Bioinformatics · doi:10.1093/bioinformatics/btaf107 · Cited by 56 · see citing works
“Additionally, the bound conformations can still be somewhat flexible, especially the flanking regions surrounding a more tightly bound region (Bugge et al. 2020). ipTM (and a confidence metric, defined as a weighted sum of ipTM and pTM) is a frequently used score for assessing docked…”
Intrinsic and extrinsic regulators of Aux/IAA protein degradation dynamics
de Figueiredo, M. R. A., & Strader, L. C. (2022) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2022.06.004 · Cited by 55 · see citing works
Intrinsically disordered proteins: Ensembles at the limits of Anfinsen's dogma
Kulkarni, P., Leite, V. B. P., Roy, S., Bhattacharyya, S., Mohanty, A. R., Achuthan, S., Singh, D., Appadurai, R., Govindan Rangarajan, C., Weninger, K., et al. (2022) · Biophysics Reviews · doi:10.1063/5.0080512 · Cited by 50 · see citing works
Langstein-Skora, I., Schmid, A., Huth, F., Shabani, D., Spechtenhauser, L., Likhodeeva, M., Kunert, F., Metzner, F. J., Emenecker, R. J., Richardson, M. O. G., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.02.10.480018 · Cited by 47 · see citing works
Theisen, F. F., Staby, L., Tidemand, F. G., O’Shea, C., Prestel, A., Willemoës, M., Kragelund, B. B., & Skriver, K. (2021) · Journal of the American Chemical Society · doi:10.1021/jacs.1c04214 · Cited by 45 · see citing works
SOURSOP: A Python Package for the Analysis of Simulations of Intrinsically Disordered Proteins
Lalmansingh, J. M., Keeley, A. T., Ruff, K. M., Pappu, R. V., & Holehouse, A. S. (2023) · Journal of Chemical Theory and Computation · doi:10.1021/acs.jctc.3c00190 · Cited by 42 · see citing works
The molecular grammar of protein disorder guiding genome-binding locations
Jonas, F., Carmi, M., Krupkin, B., Steinberger, J., Brodsky, S., Jana, T., & Barkai, N. (2023) · Nucleic Acids Research · doi:10.1093/nar/gkad184 · Cited by 43 · see citing works
Commonly asked questions about transcriptional activation domains
Udupa, A., Kotha, S. R., & Staller, M. V. (2023) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2023.102732 · Cited by 43 · see citing works
Mantonico, M. V., Leo, F. D., Quilici, G., Colley, L. S., Marchis, F. D., Crippa, M. P., Mezzapelle, R., Schulte, T. P., Zucchelli, C., Pastorello, C., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-45505-7 · Cited by 42 · see citing works
Quantifying charge state heterogeneity for proteins with multiple ionizable residues
Fossat, M. J., Posey, A. E., & Pappu, R. V. (2021) · Biophysical Journal · doi:10.1016/j.bpj.2021.11.2886 · Cited by 35 · see citing works
“Indeed, several studies have documented the important contributions made by ionizable residues to conformational (21-26), binding (27-33), and phase equilibria of IDPs (34-42).”
Intrinsic Disorder in Plant Transcription Factor Systems: Functional Implications
Salladini, E., Jørgensen, M. L. M., Theisen, F. F., & Skriver, K. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21249755 · Cited by 36 · see citing works
Mindel, V., Brodsky, S., Cohen, A., Manadre, W., Jonas, F., Carmi, M., & Barkai, N. (2023) · Nucleic Acids Research · doi:10.1093/nar/gkad1191 · Cited by 35 · see citing works
Stereochemistry in the disorder–order continuum of protein interactions
Newcombe, E. A., Due, A. D., Sottini, A., Elkjær, S., Theisen, F. F., Fernandes, C. B., Staby, L., Delaforge, E., Bartling, C. R. O., Brakti, I., et al. (2024) · Nature · doi:10.1038/s41586-024-08271-6 · Cited by 37 · see citing works
“Such strong enthalpy–entropy compensation within the core binding region imposed by dynamic flanking regions was reported previously for the N-terminal flanking region of DREB2A 40 , and the larger enthalpic contribution for DREB2A binding shows that context matters 41 .”
Subcellular localization as a driver of protein function
Sigaeva, A., Hutchings, C., Cesnik, A. J., Lilley, K. S., & Lundberg, E. (2026) · Nature reviews. Molecular cell biology · doi:10.1038/s41580-026-00947-3 · Cited by 37 · see citing works
“Secondly, subcellular localization can directly influence the stability, structure and, consequently, behaviour of a protein through changes in pH and salt concentration 84,85 , redox state 86,87 , molecular crowding 88–90 and solvating properties 91 .”
Leysen, H., Walter, D., Christiaenssen, B., Vandoren, R., Harputluoğlu, İ., Loon, N. V., & Maudsley, S. R. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222413387 · Cited by 34 · see citing works
DNA binding redistributes activation domain ensemble and accessibility in pioneer factor Sox2
Bjarnason, S., McIvor, J. A. P., Prestel, A., Demény, K. S., Bullerjahn, J. T., Kragelund, B. B., Mercadante, D., & Heidarsson, P. O. (2024) · Nature Communications · doi:10.1038/s41467-024-45847-2 · Cited by 34 · see citing works
“The classical modular view of TFs, which assumes separate functional domains unaffected by each others ’ presence, has recently come into question and at the same time, interdomain synergy and context are increasingly coming into view 38,39 .”
Pathogenic mutations of human phosphorylation sites affect protein–protein interactions
Rrustemi, T., Meyer, K., Roske, Y., Uyar, B., Akalin, A., Imami, K., Ishihama, Y., Daumke, O., & Selbach, M. (2024) · Nature Communications · doi:10.1038/s41467-024-46794-8 · Cited by 32 · see citing works
“They achieve this in a number of different ways such as the induction of structural changes in adjacent structured regions, transitioning from disorder-to-order, and/or by mediating protein-protein interactions 17 – 19 .”
BackgroundNative proline-rich motifs exploit sequence context to target actin-remodeling Ena/VASP protein ENAH
Hwang, T., Parker, S. S., Hill, S. M., Grant, R. A., Ilunga, M. W., Sivaraman, V., Mouneimne, G., & Keating, A. E. (2022) · eLife · doi:10.7554/elife.70680 · Cited by 32 · see citing works
Protein disorder and autoinhibition: The role of multivalency and effective concentration
Fenton, M. J., Gregory, E., & Daughdrill, G. W. (2023) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2023.102705 · Cited by 30 · see citing works
Multivalency emerges as a common feature of intrinsically disordered protein interactions
Sipko, E. L., Chappell, G. F., & Berlow, R. B. (2023) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2023.102742 · Cited by 31 · see citing works
Disordered Regions Flanking the Binding Interface Modulate Affinity between CBP and NCOA
Karlsson, E., Schnatwinkel, J., Paissoni, C., Andersson, E., Herrmann, C., Camilloni, C., & Jemth, P. (2022) · Journal of Molecular Biology · doi:10.1016/j.jmb.2022.167643 · Cited by 31 · see citing works
SRC homology 3 domains: multifaceted binding modules
Dionne, U., Percival, L. J., Chartier, F. J.-M., Landry, C. R., & Bisson, N. (2022) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2022.04.005 · Cited by 31 · see citing works
Orchestration of signaling by structural disorder in class 1 cytokine receptors
Seiffert, P., Bugge, K., Nygaard, M. M., Haxholm, G. W., Martinsen, J. H., Pedersen, M. N., Arleth, L., Boomsma, W., & Kragelund, B. B. (2020) · Cell Communication and Signaling · doi:10.1186/s12964-020-00626-6 · Cited by 30 · see citing works
“Furthermore, anking residues outside a SLiM and post translational modi cations (PTMs) can tune a nity and add regulatory properties assisting in the spatiotemporal orchestration of multiple binding events [13,14].”
BackgroundWang, B., Svetlov, V. V., Wolf, Y. I., Koonin, E. V., Nudler, E., & Artsimovitch, I. (2021) · mBio · doi:10.1128/mbio.01423-21 · Cited by 29 · see citing works
Shinn, M. K., Cohan, M. C., Bullock, J. L., Ruff, K. M., Levin, P. A., & Pappu, R. V. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2211178119 · Cited by 29 · see citing works
The MYC oncoprotein directly interacts with its chromatin cofactor PNUTS to recruit PP1 phosphatase
Wei, Y., Redel, C., Ahlner, A., Lemak, A. S., Johansson-Åkhe, I., Houliston, S., Kenney, T. M. G., Tamachi, A., Morad, V., Duan, S., et al. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkac138 · Cited by 28 · see citing works
“To determine whether PNUTS(1-148) interacted directly with MYC, we initially focused our analysis on the six highly conserved and regulatory MYC Box (MB) regions.”
InfluentialProtein Condensation, Cellular Organization, and Spatiotemporal Regulation of Cytoplasmic Properties
van Tartwijk, F. W., & Kaminski, C. F. (2022) · Advanced Biology · doi:10.1002/adbi.202101328 · Cited by 28 · see citing works
Kjærgaard, M., Glavina, J., & Chemes, L. B. (2020) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/bs.mie.2020.09.012 · Cited by 27 · see citing works
Schiavina, M., Salladini, E., Murrali, M. G., Tria, G., Felli, I. C., Pierattelli, R., & Longhi, S. (2020) · Scientific Reports · doi:10.1038/s41598-020-76522-3 · Cited by 27 · see citing works
Wang, D., Wu, S., Wang, D., Song, X., Yang, M., Zhang, W., Huang, S., Weng, J., Liu, Z., & Wang, W. (2022) · Chemical Science · doi:10.1039/d1sc06825c · Cited by 27 · see citing works
αα-Hub domains and intrinsically disordered proteins: A decisive combo
Bugge, K., Staby, L., Salladini, E., Falbe-Hansen, R. G., Kragelund, B. B., & Skriver, K. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.rev120.012928 · Cited by 23 · see citing works
“The context of αα -hub interactions is multifacial, including the disordered SLiM context of the partners, the modular protein scaffold of the hub, as well as the environment (139).”
Domínguez, F. D. B. P., Shiliaev, N., Lukash, T., Agback, P., Palchevska, O., Gould, J. R., Meshram, C. D., Prevelige, P. E., Green, T. J., Agback, T., et al. (2021) · Journal of Virology · doi:10.1128/jvi.00836-21 · Cited by 23 · see citing works
“Besides demonstrating unusual 386 physical characteristics, IDPs can interact with multiple proteins, mediate formation of 387 large complexes and thus, are critically involved in numerous cellular processes (46-49).”
BackgroundThe bacterial DNA sliding clamp, β-clamp: structure, interactions, dynamics and drug discovery
Simonsen, S., Søgaard, C. K., Olsen, J. G., Otterlei, M., & Kragelund, B. B. (2024) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-024-05252-w · Cited by 23 · see citing works
“However, flanking sequence regions outside the CBM as well as contacts made from other (folded) parts of the ligand, can impact binding affinity, conformation, and function as seen for other SLiMs [80].”
Sénicourt, L., le Maire, A., Allemand, F., Carvalho, J. E., Guée, L., Germain, P., Schubert, M., Bernadó, P., Bourguet, W., & Sibille, N. (2021) · Journal of Molecular Biology · doi:10.1016/j.jmb.2021.166899 · Cited by 22 · see citing works
Direct prediction of intermolecular interactions driven by disordered regionsPreprint
Ginell, G. M., Emenecker, R. J., Lotthammer, J. M., Usher, E. T., & Holehouse, A. S. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.06.03.597104 · Cited by 22 · see citing works
Staby, L., Due, A. D., Kunze, M. B. A., Jørgensen, M. L. M., Skriver, K., & Kragelund, B. B. (2021) · Journal of Molecular Biology · doi:10.1016/j.jmb.2021.167320 · Cited by 21 · see citing works
Location, location, location: Protein kinase nanoclustering for optimised signalling output
Gormal, R. S., Martínez‐Mármol, R., Brooks, A. J., & Meunier, F. A. (2023) · eLife · doi:10.7554/elife.93902 · Cited by 21 · see citing works
Naudi-Fabra, S., Elena‐Real, C. A., Vedel, I. M., Tengo, M., Motzny, K., Jiang, P., Schmieder, P., Liu, F., & Milles, S. (2024) · Nature Communications · doi:10.1038/s41467-024-50212-4 · Cited by 21 · see citing works
Proteome-scale characterisation of motif-based interactome rewiring by disease mutations
Kliche, J., Simonetti, L., Krystkowiak, I., Kuss, H., Diallo, M., Rask, E., Nilsson, J., Davey, N. E., & Ivarsson, Y. (2024) · Molecular Systems Biology · doi:10.1038/s44320-024-00055-4 · Cited by 20 · see citing works
“…likely to result in the reduction or enhancement of af fi nity, there is a growing literature reporting on the contribution of non-consensus residues in motif instances (wild-card positions) and of motif-fl anking regions to the af fi nity of interactions (Karlsson et al, 2022; Bugge et al, 2020).”
Gruber, T., Lewitzky, M., Machner, L., Weininger, U., Feller, S. M., & Balbach, J. (2021) · Journal of Molecular Biology · doi:10.1016/j.jmb.2021.167407 · Cited by 20 · see citing works
Role of charges in a dynamic disordered complex between an IDP and a folded domain
Bugge, K., Sottini, A., Ivanović, M. T., Buus, F. S., Saar, D., Fernandes, C. B., Kocher, F., Martinsen, J. H., Schuler, B., Best, R. B., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-58374-5 · Cited by 19 · see citing works
“Reviewer #2 (Remarks to the Author) In the reviewed manuscript, Bugge et al. probe the dynamic, electrostatic interactions between prothymosin alpha (an IDP) and the small, folded domain of H1.”
Use of AI-methods over MD simulations in the sampling of conformational ensembles in IDPs
Sil, S., Datta, I., & Basu, S. (2025) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2025.1542267 · Cited by 20 · see citing works
Pelham, J. F., Mosier, A. E., Altshuler, S. C., Rhodes, M. L., Kirchhoff, C. L., Fall, W. B., Mann, C., Baik, L. S., Chiu, J. C., & Hurley, J. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112376 · Cited by 17 · see citing works
Langstein-Skora, I., Schmid, A., Huth, F., Shabani, D., Spechtenhauser, L., Likhodeeva, M., Kunert, F., Metzner, F. J., Emenecker, R. J., Richardson, M. O. G., et al. (2026) · Nature Cell Biology · doi:10.1038/s41556-025-01867-8 · Cited by 15 · see citing works
“The importance of context in relation to motif function has been seen in other systems 61,82,110 .”
Evolution of SLiM-mediated hijack functions in intrinsically disordered viral proteins
Glavina, J., Palópoli, N., & Chemes, L. B. (2022) · Essays in Biochemistry · doi:10.1042/ebc20220059 · Cited by 15 · see citing works
“The close inspection of host and viral SLiMs indicates that fine-tuning of binding affinity and specificity occurs at multiple levels [101] which include changes in core [67], wildcard [70,102] and flanking [72,103] residues (Figure 4) as well as conformational preferences such as secondary…”
BackgroundIntrinsic disorder and flexibility in proteins: a challenge for structural biology and drug design
Zanotti, G. (2023) · Crystallography Reviews · doi:10.1080/0889311x.2023.2208518 · Cited by 15 · see citing works
“All these factors are analysed and discussed in reference [86], and examples are reported.”
BackgroundAllosteric control of dynamin-related protein 1 through a disordered C-terminal Short Linear Motif
Pérez-Jover, I., Rochon, K., Hu, D., Mahajan, M. K., Mohan, P. M., Santos-Pérez, I., Gisasola, J. O., Galvez, J. M. M., Agirre, J., Qi, X., et al. (2024) · Nature Communications · doi:10.1038/s41467-023-44413-6 · Cited by 15 · see citing works
“1a, b) that, unlike other IDRs in Drp1, is highly conserved among metazoans (Supplementary Fig.”
BackgroundInfluentialDesign of functional intrinsically disordered proteins
Garg, A., Foutel, N. S. G., Gielnik, M. B., & Kjærgaard, M. (2024) · Protein Engineering Design and Selection · doi:10.1093/protein/gzae004 · Cited by 15 · see citing works
Synergies of Single Molecule Fluorescence and NMR for the Study of Intrinsically Disordered Proteins
Naudi-Fabra, S., Blackledge, M. J., & Milles, S. (2021) · Biomolecules · doi:10.3390/biom12010027 · Cited by 14 · see citing works
Putta, S., Álvarez, L., Lüdtke, S., Sehr, P. A., Müller, G. A., Fernandez, S. M., Tripathi, S. M., Lewis, J., Gibson, T. J., Chemes, L. B., et al. (2022) · Structure · doi:10.1016/j.str.2022.05.019 · Cited by 14 · see citing works
A context-dependent and disordered ubiquitin-binding motif
Dreier, J. E., Prestel, A., Martins, J., Brøndum, S. S., Nielsen, O., Garbers, A. E., Suga, H., Boomsma, W., Rogers, J. M., Hartmann-Petersen, R., et al. (2022) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-022-04486-w · Cited by 17 · see citing works
“In some cases, a SLiM alone may not represent the entire binding event, and the context of the disordered chain can impact the interaction both positively and negatively [25, 71].”
Ubiquitin Interacting Motifs: Duality Between Structured and Disordered Motifs
Lambrughi, M., Maiani, E., Fas, B. A., Shaw, G. S., Kragelund, B. B., Lindorff‐Larsen, K., Teilum, K., Invernizzi, G., & Papaleo, E. (2021) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2021.676235 · Cited by 13 · see citing works
“Although individual SLiMs are short and mostly participate in transient interactions, they are essential to protein binding specificity and function (Bugge et al., 2020; Kumar et al., 2020).”
BackgroundFunctional roles and cancer variants of the bifunctional glycosylase NEIL2
Hua, A., & Sweasy, J. B. (2023) · Environmental and Molecular Mutagenesis · doi:10.1002/em.22555 · Cited by 12 · see citing works
“This particular missense mutation occurs in the NEIL2 disordered region, which is known to participate in protein – protein interactions (Bugge et al., 2020).”
The MDMX Acidic Domain Uses Allovalency to Bind Both p53 and MDMX
Fenton, M. J., Borcherds, W. M., Chen, L., Anbanandam, A., Levy, R., Chen, J., & Daughdrill, G. W. (2022) · Journal of Molecular Biology · doi:10.1016/j.jmb.2022.167844 · Cited by 12 · see citing works
Jankowski, M. S., Griffith, D., Shastry, D. G., Pelham, J. F., Ginell, G. M., Thomas, J., Karande, P., Holehouse, A. S., & Hurley, J. M. (2024) · Nature Communications · doi:10.1038/s41467-024-47761-z · Cited by 23 · see citing works
Protein binding and folding through an evolutionary lens
Jemth, P. (2025) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2024.102980 · Cited by 11 · see citing works
MUL1‐RING recruits the substrate, p53‐TAD as a complex with UBE2D2–UB conjugate
Lee, M., Lee, S.-O., Choi, J., Ryu, M., Lee, M., Kim, J., Hwang, E., Lee, C., Chi, S., & Ryu, K. (2022) · FEBS Journal · doi:10.1111/febs.16360 · Cited by 11 · see citing works
Fagerberg, E., Lenton, S., Nylander, T., Seydel, T., & Skepö, M. (2022) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.1c08976 · Cited by 11 · see citing works
The Structure of the Drp1 Lattice on Membrane
Peng, R., Rochon, K., Hutson, A. N., Stagg, S. M., & Mears, J. A. (2025) · Journal of Molecular Biology · doi:10.1016/j.jmb.2025.169125 · Cited by 12 · see citing works
“42,43 We tested the influence of the MoRF-1 region on the Drp1 lattice.”
Evolution of A bHLH Interaction Motif
Millard, P. S., Kragelund, B. B., & Burow, M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22010447 · Cited by 10 · see citing works
Structural properties of the HNF-1A transactivation domain
Kind, L., Driver, M., Raasakka, A., Onck, P. R., Njølstad, P. R., Arnesen, T., & Kursula, P. (2023) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2023.1249939 · Cited by 10 · see citing works
“IDRs frequently harbor SLiMs, which are sequence elements of 6 - 12 residues that mediate the binding to folded interaction partners or promote LLPS by partaking in multivalent interactions (64).”
BackgroundShitaye, G., Ventserova, N., D’Abrosca, G., Dragone, M., Maina, E. W., Fattorusso, R., Iacovino, R., Russo, L., Isernia, C., & Malgieri, G. (2025) · Frontiers in Chemistry · doi:10.3389/fchem.2025.1597656 · Cited by 10 · see citing works
Staby, L., Kemplen, K. R., Stein, A., Ploug, M., Clarke, J., Skriver, K., Heidarsson, P. O., & Kragelund, B. B. (2020) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-020-03639-z · Cited by 10 · see citing works
Hidden Multivalency in Phosphatase Recruitment by a Disordered AKAP Scaffold
Watson, M. L., Almeida, T., Ray, A., Hanack, C., Elston, R., Btesh, J., McNaughton, P. A., & Stott, K. M. (2022) · Journal of Molecular Biology · doi:10.1016/j.jmb.2022.167682 · Cited by 10 · see citing works
Gurumoorthy, V., Shrestha, U. R., Zhang, Q., Pingali, S. V., Boder, E. T., Urban, V. S., Smith, J. C., Petridis, L., & O’Neill, H. (2023) · Biomacromolecules · doi:10.1021/acs.biomac.2c01158 · Cited by 10 · see citing works
Lemieux, P., Bradley, D. T. C., Dubé, A. K., Dionne, U., & Landry, C. R. (2023) · Genetics · doi:10.1093/genetics/iyad175 · Cited by 8 · see citing works
“Furthermore, the mechanisms behind the contribution of disordered regions to PPI are also undefined, but the modifications of these regions, as we did by replacing the binding motif, can also affect binding in unexpected ways (Bugge et al. 2020).”
BackgroundStm1 regulates Ifh1 activity revealing crosstalk between ribosome biogenesis and ribosome dormancy
Bianco, E., Bonassera, M., Uliana, F., Tilma, J., Winkler, M., Zencir, S., Gossert, A. D., Oborská‐Oplová, M., Dechant, R. C., Hugener, J., et al. (2025) · Molecular Cell · doi:10.1016/j.molcel.2025.04.008 · Cited by 10 · see citing works
Martinsen, J. H., Saar, D., Fernandes, C. B., Schuler, B., Bugge, K., & Kragelund, B. B. (2022) · Protein Science · doi:10.1002/pro.4281 · Cited by 9 · see citing works
“The function and native conformation of protein domains are often effected by their full-chain context, 37 – 39 and accumulating evidence suggests that the binding mode of the GD in the nucleosome is influenced by its disordered tails.”
BackgroundLuo, S., Wohl, S., Zheng, W., & Yang, S. (2023) · Biomolecules · doi:10.3390/biom13030530 · Cited by 9 · see citing works
Mihalič, F., Arcila, D., Pettersson, M. E., Farkhondehkish, P., Andersson, E., Andersson, L., Betancur‐R, R., & Jemth, P. (2024) · Molecular Biology and Evolution · doi:10.1093/molbev/msae018 · Cited by 9 · see citing works
“However, recent data suggested that flanking disordered regions of the binding motif may modulate affinity (Bugge et al. 2020; Theisen et al. 2021; Karlsson et al. 2022).”
BackgroundMetabotropic Glutamate Receptors at Ribbon Synapses in the Retina and Cochlea
Klotz, L., & Enz, R. (2022) · Cells · doi:10.3390/cells11071097 · Cited by 8 · see citing works
Biallelic variants in SNUPN cause a limb girdle muscular dystrophy with myofibrillar-like features
Iruzubieta, P., Damborenea, A., Ioghen, M. R., Bajew, S., Fernández‐Torrón, R., Töpf, A., Herrero-Reiriz, Á., Epure, D., Vill, K., Hernández‐Laín, A., et al. (2024) · Brain · doi:10.1093/brain/awae046 · Cited by 8 · see citing works
“15 Specifically, the IDR may act as a swinging arm 57 that permits high amplitude motions required for binding or as a flanking region 58 to the folded domains.”
BackgroundKolonko, M., Uversky, V. N., & Greb‐Markiewicz, B. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22062868 · Cited by 8 · see citing works
“Interestingly, protein-protein interaction (PPI) could lead to LLPS formation, which enable the partition of specific functions, but in contrast LLPS may also prevent from protein interactions [22,23][24].”
BackgroundDisordered proteins mitigate the temperature dependence of site-specific binding free energies
Thole, J. F., Waudby, C. A., & Pielak, G. J. (2023) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2023.102984 · Cited by 8 · see citing works
Karlsson, E., Ottoson, C., Ye, W., Andersson, E., & Jemth, P. (2023) · Biochemistry · doi:10.1021/acs.biochem.3c00285 · Cited by 8 · see citing works
Engineering intrinsically disordered regions for guiding genome navigation
Liu, J., Kumar, D. K., Hurieva, B., Jonas, F., & Barkai, N. (2026) · Molecular Cell · doi:10.1016/j.molcel.2026.01.019 · Cited by 7 · see citing works
- Authors
- Bugge, K., Brakti, I., Fernandes, C. B., Dreier, J. E., Lundsgaard, J. E., Olsen, J. G., Skriver, K., & Kragelund, B. B.
- Affiliations
- University of Copenhagen (DK)
- Corresponding author
- Skriver, Karen
- Kragelund, Birthe B.
- ORCID
- Venue
- Frontiers in Molecular Biosciences
- Publisher
- Frontiers Media SA
- Published
- 2020-06-16
- Volume
- 7
- Pages
- 110-110
- ISSN
- 2296-889X (ISSN-L)
- PMC
- PMC7308724
- OpenAlex
- W3036355682
- Cited by
- 155
- References
- 159
- Citations by year
- 2026: 16 · 2025: 21 · 2024: 20 · 2023: 31 · 2022: 34 · 2021: 24 · 2020: 9
- FWCI
- 2.35
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Molecular Biosciences (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Novo Nordisk Fonden
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Interaction Studies and Fluorescence Analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › 14-3-3 protein interactions
- Keywords
- protein-protein interaction, intrinsically disordered proteins, structural disorder, flanking regions, context-dependent interactions, short linear motifs, multivalency, charge clusters, hydrophobic patch, allosteric regulation, feedback regulation, protein-protein interaction network, drug discovery
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