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

139 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

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Intrinsically Disordered Proteins
Burial
tau Proteins
Molecular Chaperones
Structural Models
Protein Folding
Substrates
Substrate Specificity
Protein folding
Agglomeration

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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
Karagöz, G. Elif ; Duarte, Afonso M S ; Akoury, Elias ; Ippel, Hans ; Biernat, Jacek ; Morán Luengo, Tania ; Radli, Martina ; Didenko, Tatiana ; Nordhues, Bryce A. ; Veprintsev, Dmitry B. ; Dickey, Chad A. ; Mandelkow, Eckhard ; Zweckstetter, Markus ; Boelens, Rolf ; Madl, Tobias ; Rüdiger, Stefan G D. / Hsp90-tau complex reveals molecular basis for specificity in chaperone action. In: Cell. 2014 ; Vol. 156, No. 5. pp. 963-974.
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Karagöz, GE, Duarte, AMS, 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, SGD 2014, 'Hsp90-tau complex reveals molecular basis for specificity in chaperone action', Cell, vol. 156, no. 5, pp. 963-974. https://doi.org/10.1016/j.cell.2014.01.037

Hsp90-tau complex reveals molecular basis for specificity in chaperone action. / Karagöz, G. Elif; Duarte, Afonso M S; Akoury, Elias; Ippel, Hans; Biernat, Jacek; Morán Luengo, Tania; Radli, Martina; Didenko, Tatiana; Nordhues, Bryce A.; Veprintsev, Dmitry B.; Dickey, Chad A.; Mandelkow, Eckhard; Zweckstetter, Markus; Boelens, Rolf; Madl, Tobias; Rüdiger, Stefan G D.

In: Cell, Vol. 156, No. 5, 27.02.2014, p. 963-974.

Research output: Contribution to journalArticle

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AU - Karagöz, G. Elif

AU - Duarte, Afonso M S

AU - Akoury, Elias

AU - Ippel, Hans

AU - Biernat, Jacek

AU - Morán Luengo, Tania

AU - Radli, Martina

AU - Didenko, Tatiana

AU - Nordhues, Bryce A.

AU - Veprintsev, Dmitry B.

AU - Dickey, Chad A.

AU - Mandelkow, Eckhard

AU - Zweckstetter, Markus

AU - Boelens, Rolf

AU - Madl, Tobias

AU - Rüdiger, Stefan G D

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JF - Cell

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Karagöz GE, Duarte AMS, Akoury E, Ippel H, Biernat J, Morán Luengo T et al. Hsp90-tau complex reveals molecular basis for specificity in chaperone action. Cell. 2014 Feb 27;156(5):963-974. https://doi.org/10.1016/j.cell.2014.01.037