A common conformationally coupled ATPase mechanism for yeast and human cytoplasmic HSP90s.

ABSTRACT: The conformationally coupled mechanism by which ATP is utilized by yeast Hsp90 is now well characterized. In contrast, ATP utilization by human Hsp90s is less well studied, and appears to operate differently. To resolve these conflicting models, we have conducted a side-by-side biochemical analysis in a series of mutant yeast and human Hsp90s that have been both mechanistically and structurally characterized with regard to the crystal structure of the yeast Hsp90 protein. We show that each monomer of the human Hsp90 dimer is mutually dependent on the other for ATPase activity. Fluorescence studies confirmed that the N-terminal domains of Hsp90beta come into close association with each other. Mutations that directly affect the conformational dynamics of the ATP-lid segment had marked effect

SUBMITTER: Vaughan CK 

PROVIDER: S-EPMC2702006 | biostudies-literature | 2009 Jan

REPOSITORIES: biostudies-literature