University of Sussex
Browse
1-s2.0-S1097276503000650-main.pdf (611.57 kB)

Structural and functional analysis of the middle segment of hsp90: implications for ATP hydrolysis and client protein and cochaperone interactions

Download (611.57 kB)
journal contribution
posted on 2023-06-08, 14:42 authored by Philipe Meyer, Chrisostomos ProdromouChrisostomos Prodromou, Bin Hu, Cara Vaughan, S Mark Roe, Barry Panaretou, Peter W Piper, Laurence PearlLaurence Pearl
Activation of client proteins by the Hsp90 molecular chaperone is dependent on binding and hydrolysis of ATP, which drives a molecular clamp via transient dimerization of the N-terminal domains. The crystal structure of the middle segment of yeast Hsp90 reveals considerable evolutionary divergence from the equivalent regions of other GHKL protein family members such as MutL and GyrB, including an additional domain of new fold. Using the known structure of the N-terminal nucleotide binding domain, a model for the Hsp90 dimer has been constructed. From this structure, residues implicated in the ATPase-coupled conformational cycle and in interactions with client proteins and the activating cochaperone Aha1 have been identified, and their roles functionally characterized in vitro and in vivo.

History

Publication status

  • Published

File Version

  • Published version

Journal

Molecular Cell

ISSN

1097-2765

Publisher

Elsevier

Issue

3

Volume

11

Page range

647-658

Department affiliated with

  • Biochemistry Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2015-02-25

First Open Access (FOA) Date

2015-02-25

First Compliant Deposit (FCD) Date

2015-02-25