Hsp90-tau complex reveals molecular basis for specificity in chaperone action

G. Elif Karagöz, Afonso M S Duarte, Elias Akoury, Hans Ippel, Jacek Biernat, Tania Morán Luengo, Martina Radli, Tatiana Didenko, Bryce A. Nordhues, Dmitry B. Veprintsev, Chad A. Dickey, Eckhard Mandelkow, Markus Zweckstetter, Rolf Boelens, Tobias Madl, Stefan G D Rüdiger

Research output: Contribution to journalArticle

150 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)963-974
Number of pages12
JournalCell
Volume156
Issue number5
DOIs
Publication statusPublished - 27 Feb 2014

Fingerprint Dive into the research topics of 'Hsp90-tau complex reveals molecular basis for specificity in chaperone action'. Together they form a unique fingerprint.

  • Cite this

    Karagöz, G. E., Duarte, A. M. S., Akoury, E., Ippel, H., Biernat, J., Morán Luengo, T., ... Rüdiger, S. G. D. (2014). Hsp90-tau complex reveals molecular basis for specificity in chaperone action. Cell, 156(5), 963-974. https://doi.org/10.1016/j.cell.2014.01.037