The DOI matches its Crossref record; 68 of the 68 references it cites were found in a registry or an index.
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.
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.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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
Experimental — accuracy not yet measuredIn the citing paper
“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]
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
Cites
NMRPipe: A multidimensional spectral processing system based on UNIX pipes
Delaglio, F., Grzesiek, S., Vuister, G. W., Zhu, G., Pfeifer, J., & Bax, A. (1995) · Journal of Biomolecular NMR · doi:10.1007/bf00197809 · Cited by 15,961 · cited 2×
“Spectra were processed with NMRPipe (Delaglio et al., 1995) and analyzed using CcpNMR Analysis (Vranken et al., 2005).”
MethodElectrostatics of nanosystems: Application to microtubules and the ribosome
Baker, N., Sept, D., Joseph, S., Holst, M., & McCammon, J. A. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.181342398 · Cited by 7,125
Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid β-peptide
Haass, C., & Selkoe, D. J. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2101 · Cited by 4,744 · cited 2×
“The Hsp90-Tau Interaction and Therapeutic Treatment of Alzheimer Disease Aggregation of the Tau microtubule binding region causes Alzheimer disease (Haass and Selkoe, 2007; Kosik et al., 1986).”
BackgroundMolecular chaperones in protein folding and proteostasis
Hartl, F. U., Bracher, A., & Hayer-Hartl, M. (2011) · Nature · doi:10.1038/nature10317 · Cited by 3,381 · cited 5×
“in Chaperone Action G. Elif Karagöz,1,2 Afonso M.S. Duarte,1,3 Elias Akoury,4 Hans Ippel,5,6 Jacek Biernat,7 Tania Morán Luengo,1 Martina Radli,1 Tatiana Didenko,1,15 Bryce A. Nordhues,8 Dmitry B. Veprintsev,9 Chad A. Dickey,8 EckhardMandelkow,7,10 Markus Zweckstetter,4,11,12 Rolf Boelens,5 Tobias Madl,5,13,14,* and…”
BackgroundInfluentialThe CCPN data model for NMR spectroscopy: Development of a software pipeline
Vranken, W., Boucher, W., Stevens, T. J., Fogh, R. H., Pajon, A., Llinás, M., Ulrich, E. L., Markley, J. L., Ionides, J., & Laue, E. D. (2005) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.20449 · Cited by 3,222 · cited 1×
“Spectra were processed with NMRPipe (Delaglio et al., 1995) and analyzed using CcpNMR Analysis (Vranken et al., 2005).”
MethodDolinsky, T. J., Czodrowski, P., Li, H., Nielsen, J., Jensen, J. H., Klebe, G., & Baker, N. A. (2007) · Nucleic Acids Res. · doi:10.1093/nar/gkm276 · Cited by 2,018
Tau Suppression in a Neurodegenerative Mouse Model Improves Memory Function
SantaCruz, K., Lewis, J., Spires, T., Paulson, J., Kotilinek, L., Ingelsson, M., Guimaraes, A., DeTure, M., Ramsden, M., McGowan, E., et al. (2005) · Science · doi:10.1126/science.1113694 · Cited by 2,014 · cited 1×
“Recent work suggests that Tau amyloid formation may actually be a protectivemechanism that allows potentially toxic Tau intermediates to self-chaperone and sequester themselves into less toxic entities within long-lived neurons (Eisenberg and Jucker, 2012; Oddo et al., 2004; Santacruz et al., 2005).”
BackgroundReducing Endogenous Tau Ameliorates Amyloid ß-Induced Deficits in an Alzheimer's Disease Mouse Model
Roberson, E. D., Scearce-Levie, K., Palop, J. J., Yan, F., Cheng, I. H., Wu, T., Gerstein, H., Yu, G.-Q., & Mucke, L. (2007) · Science · doi:10.1126/science.1141736 · Cited by 1,892 · cited 1×
“It also accumulates abnormally in brain tissue of Alzheimer disease patients and is closely linkedwith neuronal toxicity in this most commonneurodegenerative disease (Ittner et al., 2010; Roberson et al., 2007).”
Dendritic Function of Tau Mediates Amyloid-β Toxicity in Alzheimer's Disease Mouse Models
Ittner, L. M., Ke, Y. D., Delerue, F., Bi, M., Gladbach, A., van Eersel, J., Wölfing, H., Chieng, B. C., Christie, M. J., Napier, I. A., et al. (2010) · Cell · doi:10.1016/j.cell.2010.06.036 · Cited by 1,821 · cited 1×
“It also accumulates abnormally in brain tissue of Alzheimer disease patients and is closely linkedwith neuronal toxicity in this most commonneurodegenerative disease (Ittner et al., 2010; Roberson et al., 2007).”
HSP90 at the hub of protein homeostasis: emerging mechanistic insights
Taipale, M., Jarosz, D. F., & Lindquist, S. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2918 · Cited by 1,818 · cited 2×
“The substrate pool of Hsp90 does not share a common sequence or structural motif (Taipale et al., 2010, 2012).”
Background
Cited by
Sorted by citations
Tau in physiology and pathology
Wang, Y., & Mandelkow, E. (2016) · Nature Reviews Neuroscience · doi:10.1038/nrn.2015.1 · Cited by 2,251
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
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 1,477
“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
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 521
Metadata
- 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
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › 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
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
