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Open Access Green as soon as Postprint is submitted to ZB.
Hsp90-tau complex reveals molecular basis for specificity in chaperone action.
Cell 156, 963-974 (2014)
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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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Paired Helical Filaments; Escherichia-coli Hsp90; N-terminal Domain; X-ray-scattering; Nmr-spectroscopy; Tau-protein; Crystal-structure; Structural-analysis; Intrinsic Disorder; Quality-control
ISSN (print) / ISBN
0092-8674
e-ISSN
1097-4172
Journal
Cell
Quellenangaben
Volume: 156,
Issue: 5,
Pages: 963-974
Publisher
Cell Press
Publishing Place
Cambridge, Mass.
Reviewing status
Peer reviewed
Institute(s)
Institute of Structural Biology (STB)