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

Meyer, Philipe, Prodromou, Chrisostomos, Hu, Bin, Vaughan, Cara, Roe, S Mark, Panaretou, Barry, Piper, Peter W and Pearl, Laurence H (2003) Structural and functional analysis of the middle segment of hsp90: implications for ATP hydrolysis and client protein and cochaperone interactions. Molecular Cell, 11 (3). pp. 647-658. ISSN 1097-2765

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Abstract

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.

Item Type: Article
Keywords: Adenosine Triphosphatases/metabolism Adenosine Triphosphate/metabolism Amino Acid Sequence Binding Sites Cell Division Crystallography, X-Ray DNA Gyrase/metabolism Dimerization Dose-Response Relationship, Drug Escherichia coli Proteins/metabolism Fungal Proteins/chemistry HSP90 Heat-Shock Proteins/*chemistry/*metabolism Hydrolysis Models, Molecular Molecular Sequence Data Mutation Oncogene Protein pp60(v-src)/metabolism Phenotype Protein Binding Protein Conformation Protein Structure, Tertiary Structure-Activity Relationship Temperature
Schools and Departments: School of Life Sciences > Biochemistry
Subjects: Q Science > QD Chemistry > QD0241 Organic chemistry > QD0415 Biochemistry
Q Science > QD Chemistry > QD0901 Crystallography
Depositing User: Chrisostomos Prodromou
Date Deposited: 25 Feb 2015 07:01
Last Modified: 14 Mar 2017 05:33
URI: http://sro.sussex.ac.uk/id/eprint/44340

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