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SHR Neuro Cancer Cardio Lipid Metab Microb

Karagöz, GE; Duarte, AM; Akoury, E; Ippel, H; Biernat, J; Morán Luengo, T; Radli, M; Didenko, T; Nordhues, BA; Veprintsev, DB; Dickey, CA; Mandelkow, E; Zweckstetter, M; Boelens, R; Madl, T; Rüdiger, SG.
Hsp90-Tau complex reveals molecular basis for specificity in chaperone action.
Cell. 2014; 156(5): 963-974. Doi: 10.1016/j.cell.2014.01.037 [OPEN ACCESS]
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Leading authors Med Uni Graz: Madl Tobias
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Abstract:: 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. Copyright © 2014 Elsevier Inc. All rights reserved.
Find related publications in this database (using NLM MeSH Indexing): Alzheimer Disease - drug therapy; Amino Acid Sequence -; HSP90 Heat-Shock Proteins - chemistry HSP90 Heat-Shock Proteins - metabolism; Humans -; Models, Molecular -; Molecular Sequence Data -; Protein Folding -; Scattering, Small Angle -; X-Ray Diffraction -; tau Proteins - chemistry tau Proteins - metabolism