Structural Basis of Interdomain Communication in the Hsc70 Chaperone

Overview

Journal Mol Cell

Publisher Cell Press

Specialty Cell Biology

Date 2005 Nov 26

PMID 16307916

Citations 135

Authors

Jianwen Jiang

Kondury Prasad

Eileen M Lafer

Rui Sousa

Affiliations

Soon will be listed here.

Abstract

Hsp70 family proteins are highly conserved chaperones involved in protein folding, degradation, targeting and translocation, and protein complex remodeling. They are comprised of an N-terminal nucleotide binding domain (NBD) and a C-terminal protein substrate binding domain (SBD). ATP binding to the NBD alters SBD conformation and substrate binding kinetics, but an understanding of the mechanism of interdomain communication has been hampered by the lack of a crystal structure of an intact chaperone. We report here the 2.6 angstroms structure of a functionally intact bovine Hsc70 (bHsc70) and a mutational analysis of the observed interdomain interface and the immediately adjacent interdomain linker. This analysis identifies interdomain interactions critical for chaperone function and supports an allosteric mechanism in which the interdomain linker invades and disrupts the interdomain interface when ATP binds.

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