Intra- and intermonomer interactions are required to synergistically facilitate ATP hydrolysis in Hsp90.

ABSTRACT: Nucleotide-dependent conformational changes of the constitutively dimeric molecular chaperone Hsp90 are integral to its molecular mechanism. Recent full-length crystal structures (Protein Data Bank codes 2IOQ, 2CG9, AND 2IOP) of Hsp90 homologs reveal large scale quaternary domain rearrangements upon the addition of nucleotides. Although previous work has shown the importance of C-terminal domain dimerization for efficient ATP hydrolysis, which should imply cooperativity, other studies suggest that the two ATPases function independently. Using the crystal structures as a guide, we examined the role of intra- and intermonomer interactions in stabilizing the ATPase activity of a single active site within an intact dimer. This was accomplished by creating heterodimers that allow us to differen

SUBMITTER: Cunningham CN 

PROVIDER: S-EPMC2475720 | biostudies-literature | 2008 Jul

REPOSITORIES: biostudies-literature