The DOI matches its Crossref record.
Molecular discrimination of structurally equivalent Lys 63‐linked and linear polyubiquitin chains
Open accessAbstract
At least eight types of ubiquitin chain exist, and individual linkages affect distinct cellular processes. The only distinguishing feature of differently linked ubiquitin chains is their structure, as polymers of the same unit are chemically identical. Here, we have crystallized Lys 63‐linked and linear ubiquitin dimers, revealing that both adopt equivalent open conformations, forming no contacts between ubiquitin molecules and thereby differing significantly from Lys 48‐linked ubiquitin chains. We also examined the specificity of various deubiquitinases (DUBs) and ubiquitin‐binding domains (UBDs). All analysed DUBs, except CYLD, cleave linear chains less efficiently compared with other chain types, or not at all. Likewise, UBDs can show chain specificity, and are able to select distinct linkages from a ubiquitin chain mixture. We found that the UBAN (ubiquitin binding in ABIN and NEMO) motif of NEMO (NF‐κB essential modifier) binds to linear chains exclusively, whereas the NZF (Npl4 zinc finger) domain of TAB2 (TAK1 binding protein 2) is Lys 63 specific. Our results highlight remarkable specificity determinants within the ubiquitin system.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cited by
Komander, D., & Rape, M. (2012) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060310-170328 · Cited by 3,679
Self-citationBreaking the chains: structure and function of the deubiquitinases
Komander, D., Clague, M. J., & Urbé, S. (2009) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2731 · Cited by 1,969
Self-citationSignaling in innate immunity and inflammation
Newton, K., & Dixit, V. M. (2012) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a006049 · Cited by 1,513
The increasing complexity of the ubiquitin code
Yau, R., & Rape, M. (2016) · Nature Cell Biology · doi:10.1038/ncb3358 · Cited by 1,054
Regulation of tumour necrosis factor signalling: live or let die
Brenner, D., Blaser, H., & Mak, T. W. (2015) · Nature Reviews Immunology · doi:10.1038/nri3834 · Cited by 998
Linear ubiquitination prevents inflammation and regulates immune signalling
Gerlach, B., Cordier, S. M., Schmukle, A. C., Emmerich, C. H., Rieser, E., Haas, T. L., Webb, A. I., Rickard, J. A., Anderton, H., Wong, W. W.-L., et al. (2011) · Nature · doi:10.1038/nature09816 · Cited by 940
The emerging complexity of protein ubiquitination
Komander, D. (2009) · Biochemical Society Transactions · doi:10.1042/bst0370937 · Cited by 821
Self-citationThe role of ubiquitination in tumorigenesis and targeted drug discovery
Deng, L., Meng, T., Chen, L., Wei, W., & Wang, P. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-0107-0 · Cited by 744
Atypical ubiquitylation — the unexplored world of polyubiquitin beyond Lys48 and Lys63 linkages
Kulathu, Y., & Komander, D. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3394 · Cited by 619
Self-citationThe IκB kinase complex in NF‐κB regulation and beyond
Hinz, M., & Scheidereit, C. (2014) · The EMBO Reports · doi:10.1002/embr.201337983 · Cited by 572
Ubiquitin-like protein conjugation and the ubiquitin–proteasome system as drug targets
Bedford, L., Lowe, J., Dick, L. R., Mayer, R. J., & Brownell, J. E. (2011) · Nature Reviews Drug Discovery · doi:10.1038/nrd3321 · Cited by 563
NF-κB in inflammation and renal diseases
Zhang, H., & Sun, S.-C. (2015) · Cell & Bioscience · doi:10.1186/s13578-015-0056-4 · Cited by 383
USP8 regulates mitophagy by removing K6‐linked ubiquitin conjugates from parkin
Durcan, T. M., Tang, M. Y., Pérusse, J. R., Dashti, E. A., Aguileta, M. A., McLelland, G., Gros, P., Shaler, T. A., Faubert, D., Coulombe, B., et al. (2014) · The EMBO Journal · doi:10.15252/embj.201489729 · Cited by 375
Principles of Ubiquitin-Dependent Signaling
Oh, E., Akopian, D., & Rape, M. (2018) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-100617-062802 · Cited by 339
TBK1 and IKKε prevent TNF-induced cell death by RIPK1 phosphorylation
Lafont, E., Draber, P., Rieser, E., Reichert, M., Kupka, S., de Miguel, D., Draberova, H., von Mässenhausen, A., Bhamra, A., Henderson, S., et al. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0229-6 · Cited by 283
CYLD, A20 and OTULIN deubiquitinases in NF-κB signaling and cell death: so similar, yet so different
Lork, M., Verhelst, K., & Beyaert, R. (2017) · Cell Death & Differentiation · doi:10.1038/cdd.2017.46 · Cited by 282
The linear ubiquitin assembly complex (LUBAC) is essential for NLRP3 inflammasome activation
Rodgers, M. A., Bowman, J. W., Fujita, H., Orazio, N., Shi, M., Liang, Q., Amatya, R., Kelly, T. J., Iwai, K., Ting, J., et al. (2014) · Journal of Experimental Medicine · doi:10.1084/jem.20132486 · Cited by 247
Ubiquitin in the immune system
Zinngrebe, J., Montinaro, A., Peltzer, N., & Walczak, H. (2014) · The EMBO Reports · doi:10.1002/embr.201338025 · Cited by 227
The E3 Ligase Parkin Maintains Mitochondrial Integrity by Increasing Linear Ubiquitination of NEMO
Müller-Rischart, A. K., Pilsl, A., Beaudette, P., Patra, M., Hadian, K., Funke, M., Peis, R., Deinlein, A., Schweimer, C., Kuhn, P.-H., et al. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.01.036 · Cited by 208
Critical role of mitochondrial ubiquitination and the OPTN–ATG9A axis in mitophagy
Yamano, K., Kikuchi, R., Kojima, W., Hayashida, R., Koyano, F., Kawawaki, J., Shoda, T., Demizu, Y., Naito, M., Tanaka, K., et al. (2020) · Journal of Cell Biology · doi:10.1083/jcb.201912144 · Cited by 205
Poly-ubiquitination in TNFR1-mediated necroptosis
Dondelinger, Y., Darding, M., Bertrand, M. J. M., & Walczak, H. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2191-4 · Cited by 173
UBE3A Regulates Synaptic Plasticity and Learning and Memory by Controlling SK2 Channel Endocytosis
Sun, J., Zhu, G., Liu, Y., Standley, S., Ji, A., Tunuguntla, R., Wang, Y., Claus, C., Luo, Y., Baudry, M., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.06.023 · Cited by 131
Linear ubiquitination at a glance
Spit, M., Rieser, E., & Walczak, H. (2019) · Journal of Cell Science · doi:10.1242/jcs.208512 · Cited by 94
Long‐noncoding RNA Atrolnc‐1 promotes muscle wasting in mice with chronic kidney disease
Sun, L., Si, M., Liu, X., Choi, J. M., Wang, Y., Thomas, S. S., Peng, H., & Hu, Z. (2018) · Journal of Cachexia, Sarcopenia and Muscle · doi:10.1002/jcsm.12321 · Cited by 60
Lys63-linked ubiquitin chain adopts multiple conformational states for specific target recognition
Liu, Z., Gong, Z., Jiang, W.-X., Yang, J., Zhu, W.-K., Guo, D.-C., Zhang, W.-P., Liu, M.-L., & Tang, C. (2015) · eLife · doi:10.7554/elife.05767 · Cited by 60
The Deubiquitylase USP2 Regulates the LDLR Pathway by Counteracting the E3-Ubiquitin Ligase IDOL
Nelson, J. K., Sorrentino, V., Avagliano Trezza, R., Heride, C., Urbe, S., Distel, B., & Zelcer, N. (2016) · Circulation Research · doi:10.1161/circresaha.115.307298 · Cited by 51
Effective Molecular Dynamics from Neural Network-Based Structure Prediction Models
Jussupow, A., & Kaila, V. R. I. (2023) · Journal of Chemical Theory and Computation · doi:10.1021/acs.jctc.2c01027 · Cited by 42
BRCA1-A and BRISC: multifunctional molecular machines for ubiquitin signaling
Rabl, J. (2020) · Biomolecules · doi:10.3390/biom10111503 · Cited by 31
Strategies to Investigate Ubiquitination in Huntington's Disease
Sap, K. A., & Reits, E. A. (2020) · Frontiers in Chemistry · doi:10.3389/fchem.2020.00485 · Cited by 25
Pham, G. H., Rana, A. S. J. B., Korkmaz, E. N., Trang, V. H., Cui, Q., & Strieter, E. R. (2016) · Protein Science · doi:10.1002/pro.2834 · Cited by 21
Nawarathnage, S., Tseng, Y. J., Soleimani, S., Smith, T., Pedroza Romo, M. J., Abiodun, W. O., Egbert, C. M., Madhusanka, D., Bunn, D., Woods, B., et al. (2023) · Structure · doi:10.1016/j.str.2023.09.001 · Cited by 6
Metadata
- Authors
- Komander, D., Reyes‐Turcu, F., Licchesi, J. D. F., Odenwaelder, P., Wilkinson, K. D., & Barford, D.
- Venue
- EMBO reports
- Published
- 2009-04-17
- Volume
- 10
- Issue
- 5
- Pages
- 466-473
- ISSN
- 1469-221X (ISSN-L)
- 1469-3178
- OpenAlex
- W2127215376
- Cited by
- 572
- References
- 0
- FWCI
- 20.76
- Type
- journal article
- Language
- en
- Open access
- bronze
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
