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Trends Biochem Sci. 2015 Feb;40(2):117-25. doi: 10.1016/j.tibs.2014.12.002. Epub 2015 Jan 9.

Hsp90 interaction with clients.

Author information

1
Howard Hughes Medical Institute and Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94158, USA.
2
Cellular Protein Chemistry, Bijvoet Center for Biomolecular Research, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands. Electronic address: s.g.d.rudiger@uu.nl.

Abstract

The conserved Hsp90 chaperone is an ATP-controlled machine that assists the folding and controls the stability of select proteins. Emerging data explain how Hsp90 achieves client specificity and its role in the cellular chaperone cascade. Interestingly, Hsp90 has an extended substrate binding interface that crosses domain boundaries, exhibiting specificity for proteins with hydrophobic residues spread over a large area regardless of whether they are disordered, partly folded, or even folded. This specificity principle ensures that clients preferentially bind to Hsp70 early on in the folding path, but downstream folding intermediates bind Hsp90. Discussed here, the emerging model is that the Hsp90 ATPase does not modulate client affinity but instead controls substrate influx from Hsp70.

KEYWORDS:

Alzheimer disease; heat shock proteins; intrinsically disordered proteins; molecular chaperones; protein folding; protein–protein interactions

PMID:
25579468
DOI:
10.1016/j.tibs.2014.12.002
[Indexed for MEDLINE]

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