Hsp90-Tau complex reveals molecular basis for specificity in chaperone action
Open accessAbstract
Protein folding in the cell relies on the orchestrated action of conserved families of molecular chaperones, the Hsp70 and Hsp90 systems. Hsp70 acts early and Hsp90 late in the folding path, yet the molecular basis of this timing is enigmatic, mainly because the substrate specificity of Hsp90 is poorly understood. Here, we obtained a structural model of Hsp90 in complex with its natural disease-associated substrate, the intrinsically disordered Tau protein. Hsp90 binds to a broad region in Tau that includes the aggregation-prone repeats. Complementarily, a 106-Å-long substrate-binding interface in Hsp90 enables many low-affinity contacts. This allows recognition of scattered hydrophobic residues in late folding intermediates that remain after early burial of the Hsp70 sites. Our model resolves the paradox of how Hsp90 specifically selects for late folding intermediates but also for some intrinsically disordered proteins-through the eyes of Hsp90 they look the same.
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NMR shows Hsp90 interacts with tau only transiently in the apo state and serves as a scaffold when in complex with FKBP51.
“By NMR, Hsp90 is identified to interact with tau transiently in the apo state and function as a scaffold in complex with FKBP51”
From The structure of an Hsp90-immunophilin complex reveals cochaperone recognition of the client maturation state (2021) · cites this paper as Karagoz et al., 2014
The Results section on Hsp90 recognition of Tau reports NMR evidence of binding on an intermediate-exchange timescale, and the affinity Results section reports binding in the nucleotide-free apo state. The paper does not establish that binding occurs only in the apo state—it reports similar affinity in the ATP state—and the passages on co-chaperones do not identify FKBP51 or show Hsp90 acting as its scaffold. Page numbers are unavailable in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIn the absence of nucleotides, all clients show similar affinities in the low micromolar range for Hsp90.
“In the absence of nucleotides, all clients show similar affinities in the low micromolar range for Hsp90 (Table 1), consistent with previous studies (16, 20, 48).”
From Client binding shifts the populations of dynamic Hsp90 conformations through an allosteric network (2021) · cites this paper as [48]
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Cites
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“Crucial for the chaperone network in the cytoplasm are the ATP-driven Hsp70 and Hsp90 families (Bukau et al., 2006; Mayer, 2010).”
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BackgroundInfluentialAccelerated neurodegeneration through chaperone-mediated oligomerization of tau
Blair, L. J., Nordhues, B. A., Hill, S. E., Scaglione, K. M., O’Leary, J. C., Fontaine, S. N., Breydo, L., Zhang, B., Li, P., Wang, L., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci69003 · Cited by 322 · cited 1× · see citing works
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“…caused by the combined effects of (1) the increase in molecular weight upon complex formation, which increases transverse relaxation rates and thereby line width, and (2) the chemical exchange at the contact surface (Dekker et al., 1993; Sette et al., 1997; Wüthrich, 2003; Zuiderweg, 2002).”
BackgroundAsymmetric Activation of the Hsp90 Dimer by Its Cochaperone Aha1
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“While there is no evidence to support the first possibility, conformational asymmetry is characteristic for several previously described Hsp90 complexes (i.e., Hsp90-p23, Hsp90-Cdk4-Cdc37, and Hsp90Aha1) (Karagöz et al., 2011; Retzlaff et al., 2010; Vaughan et al., 2006).”
A molecular clamp in the crystal structure of the N-terminal domain of the yeast Hsp90 chaperone
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BackgroundMolecular chaperones, essential partners of steroid hormone receptors for activity and mobility
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BackgroundInfluentialDomain Conformation of Tau Protein Studied by Solution Small-Angle X-ray Scattering
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“…higher radius of gyration and a larger maximal extension than expected for globular proteins of the same size, consistent with its disordered nature and with previous studies (Rg = 6.8 ± 1.8 nm, Dmax = 24.9 nm; Figures 3B and 3C; Table 1) (Mylonas et al., 2008; Shkumatov et al., 2011).”
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“…provides hydrophobic interaction and negative charges similar to the other chaperone systems, it also provides a dramatically more extended substrate-binding site than any of the other chaperones (Figure 5) (Buckle et al., 1997; Rüdiger et al., 1997a; Weibe- zahn et al., 2005; Xu et al., 1997).”
BackgroundSubstrate Binding Drives Large-Scale Conformational Changes in the Hsp90 Molecular Chaperone
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“…of South Florida Health Byrd Alzheimer’s Institute, University of South Florida, Tampa, FL 33613, USA 9Laboratory of Biomolecular Research, Paul Scherrer Institut, 5232 Villigen PSI, Switzerland and Department of Biology, ETH Zürich, 8093 Zürich, Switzerland 10CAESAR Research Center,…”
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“We relate this to the fact that ATP binding alone does not induce stable conformational changes in human Hsp90, in contrast to the yeast and E. coli homologs (Figure S2) (Krukenberg et al., 2008, 2009).”
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“…caused by the combined effects of (1) the increase in molecular weight upon complex formation, which increases transverse relaxation rates and thereby line width, and (2) the chemical exchange at the contact surface (Dekker et al., 1993; Sette et al., 1997; Wüthrich, 2003; Zuiderweg, 2002).”
BackgroundInfluentialSelf-citationSolution structure of the POU-specific DNA-binding domain of Oct-1
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“…caused by the combined effects of (1) the increase in molecular weight upon complex formation, which increases transverse relaxation rates and thereby line width, and (2) the chemical exchange at the contact surface (Dekker et al., 1993; Sette et al., 1997; Wüthrich, 2003; Zuiderweg, 2002).”
BackgroundSelf-citationStructural analysis of the interaction between Hsp90 and the tumor suppressor protein p53
Hagn, F., Lagleder, S., Retzlaff, M., Rohrberg, J., Demmer, O., Richter, K., Buchner, J., & Kessler, H. (2011) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2114 · Cited by 127 · cited 1× · see citing works
“Studies that used isolated domains and/or worked at subphysiological salt conditions also implied other surface elements involved in substrate binding (Didenko et al., 2012; Hagn et al., 2011; Park et al., 2011).”
BackgroundN-terminal domain of human Hsp90 triggers binding to the cochaperone p23
Karagöz, G. E., Duarte, A. M. S., Ippel, H., Uetrecht, C., Sinnige, T., van Rosmalen, M., Hausmann, J., Heck, A. J. R., Boelens, R., & Rüdiger, S. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1011867108 · Cited by 124 · cited 1× · see citing works
“This allows recognition of scattered hydrophobic residues in late folding intermediates that remain after early burial of the Hsp70 sites.”
BackgroundSelf-citationHsp90 Inhibits α-Synuclein Aggregation by Interacting with Soluble Oligomers
Daturpalli, S., Waudby, C. A., Meehan, S., & Jackson, S. (2013) · Journal of Molecular Biology · doi:10.1016/j.jmb.2013.08.006 · Cited by 124 · cited 1× · see citing works
“This feature is not reserved for Tau alone, but for other disease-associated proteins as well, such as a-synuclein (Daturpalli et al., 2013).”
BackgroundGenest, O., Reidy, M., Street, T. O., Hoskins, J. R., Camberg, J. L., Agard, D. A., Masison, D. C., & Wickner, S. (2013) · Molecular Cell · doi:10.1016/j.molcel.2012.11.017 · Cited by 118 · cited 4× · see citing works
“For the E. coli Hsp90, some mutations in Hsp90-M and Hsp90-C were recently implicated in substrate-binding, and in fact, the mutations in Hsp90-M are close to the Tau site (Genest et al., 2013).”
BackgroundInfluentialImbalance of Hsp70 family variants fosters tau accumulation
Jinwal, U. K., Akoury, E., Abisambra, J. F., O’Leary, J. C., Thompson, A. D., Blair, L. J., Jin, Y., Bacon, J. A., Nordhues, B. A., Cockman, M. E., et al. (2012) · The FASEB Journal · doi:10.1096/fj.12-220889 · Cited by 117 · cited 5× · see citing works
“specifically bind to two short segments within this region (VQIIN and VQIVY; Figures 1C and 1F) (Jinwal et al., 2013; Sarkar et al., 2008).”
BackgroundInfluentialSelf-citationNovel insights into the mechanism of chaperone-assisted protein disaggregation
Weibezahn, J., Schlieker, C. D., Tessarz, P., Mogk, A., & Bukau, B. (2005) · Biological Chemistry · doi:10.1515/bc.2005.086 · Cited by 108 · cited 2× · see citing works
“…caused by the combined effects of (1) the increase in molecular weight upon complex formation, which increases transverse relaxation rates and thereby line width, and (2) the chemical exchange at the contact surface (Dekker et al., 1993; Sette et al., 1997; Wüthrich, 2003; Zuiderweg, 2002).”
Sarkar, M., Kuret, J., & Lee, G. S. (2008) · Journal of Neuroscience Research · doi:10.1002/jnr.21721 · Cited by 96 · cited 3× · see citing works
“The repeat region is indicated in cyan. specifically bind to two short segments within this region (275VQIIN279 and 306VQIVY310; Figures 1C and 1F) (Jinwal et al., 2013; Sarkar et al., 2008).”
Thompson, A. D., Scaglione, K. M., Prensner, J. R., Gillies, A. T., Chinnaiyan, A. M., Paulson, H. L., Jinwal, U. K., Dickey, C. A., & Gestwicki, J. E. (2012) · ACS Chemical Biology · doi:10.1021/cb3002599 · Cited by 82 · cited 3× · see citing works
“Interestingly, Hsp90 also interacts with some intrinsically disordered proteins, including the microtubule-associated protein Tau (Dickey et al., 2007; Dou et al., 2003; Miyata et al., 2011; Thompson et al., 2012).”
BackgroundInfluentialSelf-citationDynamic Interaction of Hsp90 with Its Client Protein p53
Park, S. J., Kostić, M., & Dyson, H. J. (2011) · Journal of Molecular Biology · doi:10.1016/j.jmb.2011.05.030 · Cited by 79 · cited 1× · see citing works
“Studies that used isolated domains and/or worked at subphysiological salt conditions also implied other surface elements involved in substrate binding (Didenko et al., 2012; Hagn et al., 2011; Park et al., 2011).”
BackgroundHsp90 structure and function studied by NMR spectroscopy
Didenko, T., Duarte, A. M. S., Karagöz, G. E., & Rüdiger, S. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2011.11.009 · Cited by 79 · cited 2× · see citing works
“Studies that used isolated domains and/or worked at subphysiological salt conditions also implied other surface elements involved in substrate binding (Didenko et al., 2012; Hagn et al., 2011; Park et al., 2011).”
BackgroundResultSelf-citationStructural memory of natively unfolded tau protein detected by small‐angle X‐ray scattering
Shkumatov, A. V., Chinnathambi, S., Mandelkow�, E., & Svergun, D. I. (2011) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.23033 · Cited by 69 · cited 2× · see citing works
“…higher radius of gyration and a larger maximal extension than expected for globular proteins of the same size, consistent with its disordered nature and with previous studies (Rg = 6.8 ± 1.8 nm, Dmax = 24.9 nm; Figures 3B and 3C; Table 1) (Mylonas et al., 2008; Shkumatov et al., 2011).”
InfluentialSelf-citationMiyata, Y., Koren, J., Kiray, J., Dickey, C. A., & Gestwicki, J. E. (2011) · Future Medicinal Chemistry · doi:10.4155/fmc.11.88 · Cited by 64 · cited 2× · see citing works
“…and Department of Biology, ETH Zürich, 8093 Zürich, Switzerland 10CAESAR Research Center, Ludwig-Erhard-Allee 2, 53175 Bonn, Germany 11German Center for Neurodegenerative Diseases (DZNE), 37077 Göttingen, Germany 12Center for Nanoscale Microscopy and Molecular Physiology of the Brain…”
BackgroundSelf-citationKrukenberg, K. A., Böttcher, U. M. K., Southworth, D. R., & Agard, D. A. (2009) · Protein Science · doi:10.1002/pro.191 · Cited by 57 · cited 3× · see citing works
“We relate this to the fact that ATP binding alone does not induce stable conformational changes in human Hsp90, in contrast to the yeast and E. coli homologs (Figure S2) (Krukenberg et al., 2008, 2009).”
MethodResult3D DOSY-TROSY to determine the translational diffusion coefficient of large protein complexes
Didenko, T., Boelens, R., & Rüdiger, S. (2010) · Protein Engineering Design and Selection · doi:10.1093/protein/gzq091 · Cited by 28 · cited 1× · see citing works
“Isoleucines are not involved in hydrogen bonds and therefore less sensitive to long-range structural changes when compared to backbone amide signals, as observed in previous isoleucine-based NMR analyses of Hsp90 complexes (Didenko et al., 2011, 2012; Karagöz et al., 2011).”
ResultSelf-citationSequences and topology: intrinsic disorder in the evolving universe of protein structure
Dunker, A. K., & Gough, J. (2011) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2011.04.002 · Cited by 25 · cited 1× · see citing works
“This domain differs in sequence composition from the typical IDP by a higher content in hydrophobics, a typical trigger for chaperone interaction (Figure 1E) (Dunker and Gough, 2011; Hartl et al., 2011; Uversky et al., 2009).”
Background
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Tau in physiology and pathology
Wang, Y., & Mandelkow, E. (2016) · Nature Reviews Neuroscience · doi:10.1038/nrn.2015.1 · Cited by 2,251 · see citing works
Self-citationSchopf, F. H., Biebl, M. M., & Buchner, J. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2017.20 · Cited by 1,540 · see citing works
In vivo aspects of protein folding and quality control
Balchin, D., Hayer-Hartl, M. K., & Hartl, F. U. (2016) · Science · doi:10.1126/science.aac4354 · Cited by 1,432 · see citing works
“Recent evidence suggests that Hsp90 has an extended substrate binding interface that crosses domain boundaries and exhibits specificity for proteins with exposed hydrophobic residues, independent of whether they are disordered, partly folded, or near native (113, 117, 118).”
BackgroundRosenzweig, R., Nillegoda, N. B., Mayer, M. P., & Bukau, B. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0133-3 · Cited by 1,285 · see citing works
Physicochemical Properties of Cells and Their Effects on Intrinsically Disordered Proteins (IDPs)
Theillet, F., Binolfi, A., Frembgen-Kesner, T., Hingorani, K. S., Sarkar, M., Kyne, C., Li, C., Crowley, P. B., Gierasch, L. M., Pielak, G. J., et al. (2014) · Chemical Reviews · doi:10.1021/cr400695p · Cited by 504 · see citing works
Hsp90 and Hsp70 chaperones: Collaborators in protein remodeling
Genest, O., Wickner, S., & Doyle, S. M. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.rev118.002806 · Cited by 384 · see citing works
“In contrast, Hsp90 binds to hydrophobic and charged residues exposed over a large surface area, such as natively unfolded proteins, disordered proteins, or late folding intermediates (2, 22, 23, 25, 28, 91).”
BackgroundThe Hsp70/Hsp90 Chaperone Machinery in Neurodegenerative Diseases
Lackie, R. E., Maciejewski, A., Ostapchenko, V. G., Marques-Lopes, J., Choy, W., Duennwald, M. L., Prado, V. F., & Prado, M. A. M. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00254 · Cited by 375 · see citing works
“Structural studies involving binding to intrinsically disordered tau suggest that substrate recognition occurs through low-affinity hydrophobic interactions between the client protein and a large substratebinding interface onHsp90 (Zuehlke and Johnson, 2010; Karagoz et al., 2014).”
BackgroundStructure, Function, and Regulation of the Hsp90 MachineryPreprint
Biebl, M. M., & Büchner, J. (2019) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a034017 · Cited by 308 · see citing works
“An ensemble of structural models obtained by NMR spectroscopy of the tau protein suggested contacts of the client to the NTD and MD (Karagoz et al. 2014).”
BackgroundKaragöz, G. E., Acosta‐Alvear, D., & Walter, P. (2019) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a033886 · Cited by 302 · see citing works
“…between 5 and 30 µM, which is in the same order of magnitude as those reported for most chaperones (Marcinowski et al. 2011; Street et al. 2011; Karagöz et al. 2014), and peptide binding induces the formation of IRE1 cLD oligomers as assessed by analytical ultracentrifugation analyses…”
BackgroundSelf-citationThe Hsp70–Hsp90 Chaperone Cascade in Protein Folding
Luengo, T. M., Mayer, M. P., & Rüdiger, S. (2018) · Trends in Cell Biology · doi:10.1016/j.tcb.2018.10.004 · Cited by 276 · see citing works
Self-citationRegulation of α-synuclein by chaperones in mammalian cells
Burmann, B. M., Gerez, J. A., Matečko-Burmann, I., Campioni, S., Kumari, P., Ghosh, D., Mazur, A., Aspholm, E. E., Šulskis, D., Wawrzyniuk, M., et al. (2020) · Nature · doi:10.1038/s41586-019-1808-9 · Cited by 255 · see citing works
Self-citationAn unfolded protein-induced conformational switch activates mammalian IRE1
Karagöz, G. E., Acosta‐Alvear, D., Nguyen, H. T., Lee, C. P., Feixia Chu, C., & Walter, P. (2017) · eLife · doi:10.7554/elife.30700 · Cited by 238 · see citing works
“hIRE1a cLD's affinity for peptides measured here varied between 5 and 30 mM, which is within the same order of magnitude but at the lower range of those reported for most chaperones (Karagö z et al., 2014; Marcinowski et al., 2011; Street et al., 2011) .”
InfluentialSelf-citationNMR spectroscopy captures the essential role of dynamics in regulating biomolecular function
Alderson, T. R., & Kay, L. E. (2021) · Cell · doi:10.1016/j.cell.2020.12.034 · Cited by 227 · see citing works
Structural and functional complexity of HSP90 in cellular homeostasis and disease
Chiosis, G., Digwal, C. S., Trepel, J., & Neckers, L. (2023) · Nature reviews. Molecular cell biology · doi:10.1038/s41580-023-00640-9 · Cited by 174 · see citing works
“As discussed above, HSP90 binds to clients in different conformations and establishes extensive contacts with these proteins rather than through specific motifs 23,33–36 .”
BackgroundHsp90 interaction with clients
Karagöz, G. E., & Rüdiger, S. (2015) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2014.12.002 · Cited by 203 · see citing works
“Complementary to the NMR data, SAXS data generated a low-resolution picture of the overall shape of the complex [15].”
InfluentialSelf-citationHSP90AB1: Helping the good and the bad
Haase, M., & Fitze, G. (2016) · Gene · doi:10.1016/j.gene.2015.08.063 · Cited by 179 · see citing works
“HSP90 stabilizes tau protein which forms precipitates in Alzheimer disease and other tauopathies (Karagoz et al. 2014).”
BackgroundAllosteric Modulator Discovery: From Serendipity to Structure-Based Design
Lu, S., He, X., Ni, D., & Zhang, J. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b01749 · Cited by 176 · see citing works
Mayer, M. P., & Breton, L. L. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.02.022 · Cited by 176 · see citing works
“In a recent study, Rüdiger and colleagues used NMR and SAXS to determine the Hsp90 binding site within the Tau sequence and the Tau binding site on the Hsp90 dimer (Karagöz et al., 2014).”
BackgroundMethodInfluentialAmyloidogenesis of Tau protein
Niżyński, B., Dzwolak, W., & Nieznański, K. (2017) · Protein Science · doi:10.1002/pro.3275 · Cited by 157 · see citing works
Methyl TROSY spectroscopy: A versatile NMR approach to study challenging biological systems
Schütz, S., & Sprangers, R. (2019) · Progress in Nuclear Magnetic Resonance Spectroscopy · doi:10.1016/j.pnmrs.2019.09.004 · Cited by 157 · see citing works
Folding of the Tau Protein on Microtubules
Kadavath, H., Jaremko, M., Jaremko, Ł., Biernat, J., Mandelkow, E., & Zweckstetter, M. (2015) · Angewandte Chemie International Edition · doi:10.1002/anie.201501714 · Cited by 153 · see citing works
Self-citationHsp90 Breaks the Deadlock of the Hsp70 Chaperone System
Luengo, T. M., Kityk, R., Mayer, M. P., & Rüdiger, S. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.03.028 · Cited by 151 · see citing works
“First, Hsp70 promotes protein folding while it binds to short, very hydrophobic stretches, which are required to form the hydrophobic core of the protein (R € udiger et al., 1997; Karago¨z et al., 2014).”
Self-citationMapping interactions with the chaperone network reveals factors that protect against tau aggregation
Mok, S., Condello, C., Freilich, R., Gillies, A. T., Arhar, T., Oroz, J., Kadavath, H., Julien, O., Assimon, V. A., Rauch, J. N., et al. (2018) · Nature Structural & Molecular Biology · doi:10.1038/s41594-018-0057-1 · Cited by 145 · see citing works
Self-citationThe Plasticity of the Hsp90 Co-chaperone System
Sahasrabudhe, P., Rohrberg, J., Biebl, M. M., Rutz, D. A., & Buchner, J. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.08.004 · Cited by 136 · see citing works
CCT complex restricts neuropathogenic protein aggregation via autophagy
Tanasa, M. P., Imarisio, S., Menzies, F. M., Jiménez-Sánchez, M., Siddiqi, F. H., Wu, X., Renna, M., O’Kane, C. J., Crowther, D. C., & Rubinsztein, D. C. (2016) · Nature Communications · doi:10.1038/ncomms13821 · Cited by 137 · see citing works
Experimental Milestones in the Discovery of Molecular Chaperones as Polypeptide Unfolding Enzymes
Finka, A., Mattoo, R. U. H., & Goloubinoff, P. (2016) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060815-014124 · Cited by 132 · see citing works
Progress in the Discovery and Development of Heat Shock Protein 90 (Hsp90) Inhibitors
Bhat, R., Tummalapalli, S. R., & Rotella, D. P. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm500823a · Cited by 130 · see citing works
Hsp90 activator Aha1 drives production of pathological tau aggregates
Shelton, L. B., Baker, J. D., Zheng, D., Sullivan, L. E., Solanki, P. K., Webster, J. M., Sun, Z., Sabbagh, J. J., Nordhues, B. A., Koren, J., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1707039114 · Cited by 128 · see citing works
“Of the proteins regulated by Hsp90, often referred to as “clients,” tau is one of the most thoroughly characterized (6).”
BackgroundSelf-citationA script to highlight hydrophobicity and charge on protein surfaces
Hagemans, D., van Belzen, I. A. E. M., Luengo, T. M., & Rüdiger, S. (2015) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2015.00056 · Cited by 128 · see citing works
“The analysis of the substrate recognition site of the molecular chaperone Hsp90, however, makes it evident that it is also important to consider hydrophobic contributions of residues that are otherwise polar or even charged (Karagöz et al., 2014; Karagöz and Rüdiger, 2015).”
BackgroundSelf-citationDevelopment of disease-modifying drugs for frontotemporal dementia spectrum disorders
Panza, F., Lozupone, M., Seripa, D., Daniele, A., Watling, M., Giannelli, G., & Imbimbo, B. P. (2020) · Nature Reviews Neurology · doi:10.1038/s41582-020-0330-x · Cited by 122 · see citing works
Gunawardana, C. G., Mehrabian, M., Wang, X., Mueller, I., Lubambo, I., Jonkman, J. E. N., Wang, H., & Schmitt‐Ulms, G. (2015) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m115.050724 · Cited by 119 · see citing works
“For instance, Hsp70 and Hsp90 were known to bind to relatively extended and partially overlapping tau binding epitopes, encompassing stretches of amino acids within the microtubule assembly domain and the proximal portion of the C-terminal domain (27).”
BackgroundTargeting Hsp90 and its co-chaperones to treat Alzheimer’s disease
Blair, L. J., Sabbagh, J. J., & Dickey, C. (2014) · Expert opinion on therapeutic targets · doi:10.1517/14728222.2014.943185 · Cited by 113 · see citing works
“Hsp90 recognizes structural elements of a client [45] rather than a particular primary sequence, and then allows other co-chaperones with enzymatic activity such as cis/trans peptidyl-prolyl isomerases or protein phosphatases to try and fold or repair the Hsp90-bound client.”
BackgroundSelf-citationIntrinsic 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 · see citing works
Tau Protein Squired by Molecular Chaperones During Alzheimer’s Disease
Gorantla, N. V., & Chinnathambi, S. (2018) · Journal of Molecular Neuroscience · doi:10.1007/s12031-018-1174-3 · Cited by 112 · see citing works
Therapeutic strategies for the treatment of tauopathies: Hopes and challenges
Khanna, M. R., Kovalevich, J., Lee, V. M. ‐., Trojanowski, J. Q., & Brunden, K. R. (2016) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2016.06.006 · Cited by 112 · see citing works
“[134] Karagoz GE, Duarte AM, Akoury E, Ippel H, Biernat J, Moran Luengo T, et al.”
BackgroundFolding or holding?—Hsp70 and Hsp90 chaperoning of misfolded proteins in neurodegenerative disease
Rutledge, B. S., Choy, W., & Duennwald, M. L. (2022) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2022.101905 · Cited by 110 · see citing works
“The binding of Hsp90 triggers the opening of the “paper-clip” conformation, which promotes the interaction with microtubules (39, 41).”
BackgroundInfluentialInterplay between tau and α‐synuclein liquid–liquid phase separation
Siegert, A., Rankovic, M., Favretto, F., Ukmar, T., Strohäker, T., Becker, S., & Zweckstetter, M. (2021) · Protein Science · doi:10.1002/pro.4025 · Cited by 105 · see citing works
“In addition, it contributes to the interaction of tau with the molecular chaperone Hsp90.(46) RNA also binds to the positively charged P2 region of tau.”
BackgroundSelf-citationForces Driving Chaperone Action
Koldewey, P., Stull, F. W., Horowitz, S. A., Martin, R., & Bardwell, J. C. A. (2016) · Cell · doi:10.1016/j.cell.2016.05.054 · Cited by 110 · see citing works
“Similarly, a recent structural analysis of Hsp90-Tau binding found that the Hsp90 client interaction site contained a mixture of hydrophobic and charged residues (Karagöz et al., 2014), with superficially similar properties to the mixed hydrophobic and charged folding surface of Spy.”
BackgroundMolecular chaperones and neuronal proteostasis
Smith, H., Li, W., & Cheetham, M. E. (2015) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2015.03.003 · Cited by 107 · see citing works
“Tau is a client of Hsp90, binding via its aggregation prone microtubule binding repeat region [24].”
BackgroundStructure and pro-toxic mechanism of the human Hsp90/PPIase/Tau complex
Oroz, J., Chang, B. J., Wysoczanski, P., Lee, C.-T., Pérez-Lara, Á., Chakraborty, P., Hofele, R. V., Baker, J. D., Blair, L. J., Biernat, J., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-06880-0 · Cited by 100 · see citing works
Self-citationUversky, V. N. (2014) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2014.00006 · Cited by 107 · see citing works
Ando, K., Maruko-Otake, A., Ohtake, Y., Hayashishita, M., Sekiya, M., & Iijima, K. M. (2016) · PLOS Genetics · doi:10.1371/journal.pgen.1005917 · Cited by 105 · see citing works
Hu, G., Wu, Z., Uversky, V. N., & Kurgan, L. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18122761 · Cited by 105 · see citing works
It’s not magic – Hsp90 and its effects on genetic and epigenetic variation
Zabinsky, R. A., Mason, G. A., Queitsch, C., & Jarosz, D. F. (2018) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2018.05.015 · Cited by 104 · see citing works
Dancing with the Diva: Hsp90–Client Interactions
Radli, M., & Rüdiger, S. (2018) · Journal of Molecular Biology · doi:10.1016/j.jmb.2018.05.026 · Cited by 101 · see citing works
Self-citationProtein aggregation and ER stress
Ogen‐Shtern, N., David, T. B., & Lederkremer, G. Z. (2016) · Brain Research · doi:10.1016/j.brainres.2016.03.044 · Cited by 97 · see citing works
The mechanism of Hsp90-induced oligomerizaton of Tau
Weickert, S., Wawrzyniuk, M., John, L., Rüdiger, S., & Drescher, M. (2020) · Science Advances · doi:10.1126/sciadv.aax6999 · Cited by 95 · see citing works
“Both residues are located in Tau-RD, which has been identified as the Hsp90-binding region before (25).”
InfluentialSelf-citationStructures of Large Protein Complexes Determined by Nuclear Magnetic Resonance Spectroscopy
Huang, C., & Kalodimos, C. G. (2017) · Annual Review of Biophysics · doi:10.1146/annurev-biophys-070816-033701 · Cited by 96 · see citing works
Chaperones in Neurodegeneration
Lindberg, I., Shorter, J., Wiseman, R. L., Chiti, F., Dickey, C. A., & McLean, P. J. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.2600-15.2015 · Cited by 97 · see citing works
“Tau physically interacts with Hsp90, and indeed provided the first 3D structure of a client complexed with Hsp90 (Karagöz et al., 2014).”
BackgroundSelf-citationBaughman, H. E. R., Clouser, A. F., Klevit, R. E., & Nath, A. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.m117.803411 · Cited by 94 · see citing works
Modulation of Amyloid States by Molecular ChaperonesPreprint
Wentink, A. S., Nussbaum-Krammer, C. I., & Bukau, B. (2019) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a033969 · Cited by 91 · see citing works
“As an intrinsically disordered protein, tau does not rely on these chaperones for folding; however, its interaction with chaperones is essential to regulate tau microtubule association, phosphorylation status, and degradation (Jinwal et al. 2010; Thompson et al. 2012; Karagoz et al. 2014).”
BackgroundThe Ubiquitin-Proteasome System and Molecular Chaperone Deregulation in Alzheimer’s Disease
Sulistio, Y. A., & Heese, K. (2015) · Molecular Neurobiology · doi:10.1007/s12035-014-9063-4 · Cited by 93 · see citing works
Systematic Mutant Analyses Elucidate General and Client-Specific Aspects of Hsp90 Function
Mishra, P., Flynn, J. M., Starr, T. N., & Bolon, D. N. A. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.03.046 · Cited by 86 · see citing works
Modulation of the Maladaptive Stress Response to Manage Diseases of Protein Folding
Roth, D., Hutt, D. M., Tong, J., Bouchecareilh, M., Wang, N., Seeley, T., Dekkers, J. F., Beekman, J. M., Garza, D., Drew, L., et al. (2014) · PLoS Biology · doi:10.1371/journal.pbio.1001998 · Cited by 89 · see citing works
Dahiya, V., Agam, G. N., Lawatscheck, J., Rutz, D. A., Lamb, D. C., & Büchner, J. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.03.026 · Cited by 92 · see citing works
Methyl groups as NMR probes for biomolecular interactions
Wiesner, S., & Sprangers, R. (2015) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2015.08.010 · Cited by 86 · see citing works
The therapeutic hope for HDAC6 inhibitors in malignancy and chronic disease
Batchu, S. N., Brijmohan, A. S., & Advani, A. (2016) · Clinical Science · doi:10.1042/cs20160084 · Cited by 84 · see citing works
Lee, K., Thwin, A. C., Nadel, C. M., Tse, E., Gates, S. N., Gestwicki, J. E., & Southworth, D. R. (2021) · Molecular Cell · doi:10.1016/j.molcel.2021.07.023 · Cited by 76 · see citing works
Conformational processing of oncogenic v-Src kinase by the molecular chaperone Hsp90
Boczek, E. E., Reefschläger, L. G., Dehling, M., Struller, T. J., Häusler, E., Seidl, A., Kaila, V. R. I., & Büchner, J. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1424342112 · Cited by 82 · see citing works
“The middle domain (M-domain) is involved in client binding (7, 8), and the N-terminal domain binds ATP.”
BackgroundImbalances in the Hsp90 Chaperone Machinery: Implications for Tauopathies
Shelton, L. B., Koren, J., & Blair, L. J. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00724 · Cited by 78 · see citing works
“Hsp90 binds to one of these IDPs, tau, in a broad region that includes aggregation prone areas (Karagöz et al., 2014).”
BackgroundHuck, J. D., Que, N. L., Hong, F., Li, Z., & Gewirth, D. T. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.08.079 · Cited by 73 · see citing works
“The partial client mimetic:GRP94 interaction we have observed differs from chaperonesubstrate complexes seen in previously described complexes between Hsp90β and tau (Karagoz et al., 2014) and yeast Hsp90 and the glucocorticoid receptor ligand binding domain (GRlbd) (Lorenz et al.”
BackgroundInfluentialEftekharzadeh, B., Banduseela, V. C., Chiesa, G., Martínez-Cristóbal, P., Rauch, J. N., Nath, S. R., Schwarz, D. M. C., Shao, H., Marin-Argany, M., Di Sanza, C., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-11594-y · Cited by 76 · see citing works
Uversky, V. N. (2017) · Autophagy · doi:10.1080/15548627.2017.1384889 · Cited by 76 · see citing works
Functional principles and regulation of molecular chaperones
Dahiya, V., & Büchner, J. (2018) · Advances in protein chemistry and structural biology · doi:10.1016/bs.apcsb.2018.10.001 · Cited by 75 · see citing works
Gerson, J. E., Castillo‐Carranza, D. L., & Kayed, R. (2014) · ACS Chemical Neuroscience · doi:10.1021/cn500143n · Cited by 73 · see citing works
Lupo, F., Tibaldi, E. V., Mattè, A., Sharma, A. K., Brunati, A. M., Alper, S. L., Zancanaro, C., Benati, D., Siciliano, A., Bertoldi, M., et al. (2016) · Blood · doi:10.1182/blood-2016-07-727321 · Cited by 70 · see citing works
“and autophagosomes that recognizes damaged proteins.(65,66) As shown inFigure 7A, chorea-acanthocytosis erythroblasts accumulated LAMP1 and p62 to higher levels than did healthy cells, consistent with impaired autophagy.”
BackgroundThe Unfolded Protein Response as a Guardian of the Secretory Pathway
Radanović, T., & Ernst, R. (2021) · Cells · doi:10.3390/cells10112965 · Cited by 68 · see citing works
“Whereas IRE1α’s affinity for such peptides is comparable to the range of affinities reported between molecular chaperones and their clients [112,113], it is notable that the peptide binding preference of human IRE1α and BiP are distinct [99].”
Hsp40s play complementary roles in the prevention of tau amyloid formation
Irwin, R., Faust, O., Petrovic, I. M., Wolf, S. G., Hofmann, H., & Rosenzweig, R. (2021) · eLife · doi:10.7554/elife.69601 · Cited by 66 · see citing works
Sinnige, T., Yu, A.-A., & Morimoto, R. (2020) · Advances in Experimental Medicine and Biology · doi:10.1007/978-3-030-40204-4_4 · Cited by 47 · see citing works
Molecular mechanisms of amyloid formation in living systems
Sinnige, T. (2022) · Chemical Science · doi:10.1039/d2sc01278b · Cited by 64 · see citing works
Visualizing chaperone-assisted protein folding
Horowitz, S. A., Salmon, L., Koldewey, P., Ahlstrom, L. S., Martin, R., Quan, S., Afonine, P. V., van den Bedem, H., Wang, L., Xu, Q., et al. (2016) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.3237 · Cited by 62 · see citing works
Wang, M., Shen, A., Zhang, C., Song, Z., Ai, J., Liu, H., Sun, L., Ding, J., Geng, M., & Zhang, A. (2016) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5b01106 · Cited by 62 · see citing works
Non-chaperone Proteins Can Inhibit Aggregation and Cytotoxicity of Alzheimer Amyloid β Peptide
Luo, J., Wärmländer, S. K. T. S., Gräslund, A., & Abrahams, J. P. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.574947 · Cited by 62 · see citing works
Cellular factors modulating the mechanism of tau protein aggregation
Fontaine, S. N., Sabbagh, J. J., Baker, J. D., Licha, C. R. M., Darling, A. L., & Dickey, C. A. (2015) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-015-1839-9 · Cited by 60 · see citing works
Self-citationZhuravleva, A., & Korzhnev, D. M. (2016) · Progress in Nuclear Magnetic Resonance Spectroscopy · doi:10.1016/j.pnmrs.2016.10.002 · Cited by 59 · see citing works
Client binding shifts the populations of dynamic Hsp90 conformations through an allosteric network
Lopez, A., Dahiya, V., Delhommel, F., Freiburger, L., Stehle, R., Asami, S., Rutz, D., Blair, L., Buchner, J., & Sattler, M. (2021) · Science Advances · doi:10.1126/sciadv.abl7295 · Cited by 59 · see citing works
Arginine π-stacking drives binding to fibrils of the Alzheimer protein Tau
Ferrari, L., Stucchi, R., Konstantoulea, K., van de Kamp, G., Kos, R., Geerts, W. J. C., van Bezouwen, L. S., Förster, F. G., Altelaar, M. A. F., Hoogenraad, C. C., et al. (2020) · Nature Communications · doi:10.1038/s41467-019-13745-7 · Cited by 62 · see citing works
Self-citationMechanistic basis for the recognition of a misfolded protein by the molecular chaperone Hsp90
Oroz, J., Kim, J. H., Chang, B. J., & Zweckstetter, M. (2017) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.3380 · Cited by 58 · see citing works
Self-citationHsp multichaperone complex buffers pathologically modified Tau
Moll, A., Ramirez, L. M., Ninov, M., Schwarz, J., Urlaub, H., & Zweckstetter, M. (2022) · Nature Communications · doi:10.1038/s41467-022-31396-z · Cited by 56 · see citing works
Self-citationThe Hsp90 molecular chaperone governs client proteins by targeting intrinsically disordered regions
Kolhe, J. A., Babu, N. L., & Freeman, B. (2023) · Molecular Cell · doi:10.1016/j.molcel.2023.05.021 · Cited by 58 · see citing works
Chaperone-Bound Clients: The Importance of Being Dynamic
Hiller, S. (2019) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2018.12.005 · Cited by 54 · see citing works
“Just as for the Skp–Omp complex, this model underscores the importance of multiple non-specific low-affinity contacts to build up towards a global high affinity interaction by avidity (28).”
BackgroundYu, A., Fox, S. G., Cavallini, A., Kerridge, C., O’Neill, M. J., Wolak, J., Bose, S., & Morimoto, R. I. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.ra119.007527 · Cited by 55 · see citing works
“isoforms can interact with a subset of the chaperone network to assist proper folding and prevent misfolding and aggregation (50,52-54).”
BackgroundHsp70-mediated quality control: should I stay or should I go?
Kohler, V., & Andréasson, C. (2020) · Biological Chemistry · doi:10.1515/hsz-2020-0187 · Cited by 57 · see citing works
Drepper, F., Biernat, J., Kaniyappan, S., Meyer, H. E., Mandelkow, E., Warscheid, B., & Mandelkow�, E. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.ra120.015882 · Cited by 53 · see citing works
“Finally, there are numerous examples of interactions between Tau and chaperones (81), a class that is prominent among the identified associated proteins.”
BackgroundSelf-citationDnaJC7 binds natively folded structural elements in tau to inhibit amyloid formation
Hou, Z., Wydorski, P. M., Perez, V. A., Mendoza‐Oliva, A., Ryder, B. D., Mirbaha, H., Kashmer, O. M., & Joachimiak, Ł. A. (2021) · Nature Communications · doi:10.1038/s41467-021-25635-y · Cited by 53 · see citing works
How do protein aggregates escape quality control in neurodegeneration?
Koopman, M., Ferrari, L., & Rüdiger, S. (2022) · Trends in Neurosciences · doi:10.1016/j.tins.2022.01.006 · Cited by 38 · see citing works
Self-citationHsp90: From Cellular to Organismal Proteostasis
Somogyvári, M., Khatatneh, S., & Sőti, C. (2022) · Cells · doi:10.3390/cells11162479 · Cited by 51 · see citing works
“Some clients bind to Hsp90 with a moderate affinity [42,50,51], while for other clients, the affinity is affected by Hsp90 conformation, as in the case of glucocorticoid receptors (GR).”
BackgroundProteomic analysis of protein homeostasis and aggregation
Laskowska, E., Kuczyńska‐Wiśnik, D., & Lipińska, B. (2018) · Journal of Proteomics · doi:10.1016/j.jprot.2018.12.003 · Cited by 49 · see citing works
Folding while bound to chaperones
Horowitz, S. A., Koldewey, P., Stull, F. W., & Bardwell, J. C. A. (2017) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2017.06.009 · Cited by 48 · see citing works
He, W.-T., Xue, W., Gao, Y., Hong, J.-Y., Yue, H.-W., Jiang, L.-L., & Hu, H.-Y. (2017) · Scientific Reports · doi:10.1038/s41598-017-13711-7 · Cited by 46 · see citing works
Advances towards Understanding the Mechanism of Action of the Hsp90 Complex
Prodromou, C., & Bjorklund, D. M. (2022) · Biomolecules · doi:10.3390/biom12050600 · Cited by 47 · see citing works
“Using an NMR approach, together with small angle scattering, a structural model was obtained for the interaction between Hsp90 and Tau [77].”
BackgroundMethodInfluentialCo-Chaperones in Targeting and Delivery of Misfolded Proteins to the 26S Proteasome
Abildgaard, A. B., Gersing, S. K., Larsen-Ledet, S., Nielsen, S. V., Stein, A., Lindorff‐Larsen, K., & Hartmann‐Petersen, R. (2020) · Biomolecules · doi:10.3390/biom10081141 · Cited by 44 · see citing works
“This client preference is facilitated by the large substrate-binding interface of HSP90 [118].”
BackgroundPremji, T. P., Dash, B. S., Das, S., & Chen, J. (2024) · Nanomaterials · doi:10.3390/nano14010112 · Cited by 45 · see citing works
Cesa, L. C., Shao, H., Srinivasan, S. R., Tse, E., Jain, C., Zuiderweg, E. R. P., Southworth, D. R., Mapp, A. K., & Gestwicki, J. E. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.ra117.000634 · Cited by 44 · see citing works
“Hsp90 has been reported to bind a more restricted set of ~200 kinases and transcription factors (5), but it also binds to some intrinsically disordered proteins, including tau (31,32).”
BackgroundMethodAndo, K., Oka, M., Ohtake, Y., Motoki, H., Shimizu, S., Hisanaga, S., & Iijima, K. (2016) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2016.08.053 · Cited by 40 · see citing works
Chaperones and chaperone–substrate complexes: Dynamic playgrounds for NMR spectroscopists
Burmann, B. M., & Hiller, S. (2015) · Progress in Nuclear Magnetic Resonance Spectroscopy · doi:10.1016/j.pnmrs.2015.02.004 · Cited by 40 · see citing works
“Chemical shift perturbation [102, 180, 181, 188, 189, 191, 192, 194, 204] [211, 216-219, 222] [84, 277] [91] [260, 266] [313, 314] [88, 123, 146, 151-154, 162] [233, 235] [48] [236, 244, 245, 248-250, 253]”
BackgroundResultInfluentialChaperoning shape-shifting tau in disease
Ryder, B. D., Wydorski, P. M., Hou, Z., & Joachimiak, Ł. A. (2022) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2021.12.009 · Cited by 43 · see citing works
Metamorphism in TDP-43 prion-like domain determines chaperone recognition
Carrasco, J., Antón, R., Valbuena, A., Pantoja‐Uceda, D., Mukhi, M., Hervás, R., Laurents, D. V., Gasset, M., & Oroz, J. (2023) · Nature Communications · doi:10.1038/s41467-023-36023-z · Cited by 39 · see citing works
Lorenzo, D. D. (2024) · ChemMedChem · doi:10.1002/cmdc.202400180 · Cited by 40 · see citing works
Targeting the mitochondrial chaperone TRAP1: strategies and therapeutic perspectives
Serapian, S. A., Sànchez‐Martìn, C., Moroni, E., Rasola, A., & Colombo, G. (2021) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2021.04.003 · Cited by 39 · see citing works
- Authors
- Karagöz, G. E., Duarte, A. M. S., Akoury, E., Ippel, H., Biernat, J., Morán Luengo, T., Radli, M., Didenko, T., Nordhues, B. A., Veprintsev, D. B., Dickey, C. A., Mandelkow, E., Zweckstetter, M., Boelens, R., Madl, T., & Rüdiger, S. G. D.
- Affiliations
- Howard Hughes Medical Institute (US)
- Utrecht University (NL)
- Max Planck Institute for Biophysical Chemistry (DE)
- German Center for Neurodegenerative Diseases (DE)
- University of South Florida (US)
- Paul Scherrer Institute (CH)
- University of Graz (AT)
- Corresponding author
- Madl, Tobias
- Rüdiger, Stefan G.D.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2014-02
- Volume
- 156
- Issue
- 5
- Pages
- 963-974
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC4263503
- OpenAlex
- W1993050837
- Cited by
- 318
- References
- 68
- Citations by year
- 2026: 13 · 2025: 21 · 2024: 22 · 2023: 31 · 2022: 27 · 2021: 19 · 2020: 27 · 2019: 33 · 2018: 32 · 2017: 31 · 2016: 26 · 2015: 26 · 2014: 10
- FWCI
- 12.70
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Research Publications (Maastricht University) (submittedVersion, other-oa)
- DORA PSI (Paul Scherrer Institute) (submittedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion)
- Max Planck Digital Library (submittedVersion, other-oa)
- Max Planck Digital Library (submittedVersion)
- Repository@Nottingham (University of Nottingham) (submittedVersion, cc-by)
- Site cant be reached (submittedVersion)
- DZNE Pub (submittedVersion)
- GRO (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- European Commission (261863)
- National Institute of Neurological Disorders and Stroke (R01NS073899, NS073899)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- HSP90, tau protein, molecular chaperones, protein folding, substrate specificity, intrinsically disordered proteins, HSP70, folding intermediates, hydrophobic residues
- MeSH terms
- Alzheimer Disease, Amino Acid Sequence, Humans, Models, Molecular, Molecular Sequence Data, X-Ray Diffraction, tau Proteins, Protein Folding, HSP90 Heat-Shock Proteins, Scattering, Small Angle
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