Mitotic phosphorylation regulates Hsp72 spindle localization by uncoupling ATP binding from substrate release.

ABSTRACT: Hsp72 is a member of the 70-kDa heat shock family of molecular chaperones (Hsp70s) that comprise a nucleotide-binding domain (NBD) and a substrate-binding domain (SBD) connected by a linker that couples the exchange of adenosine diphosphate (ADP) for adenosine triphosphate (ATP) with the release of the protein substrate. Mitotic phosphorylation of Hsp72 by the kinase NEK6 at Thr⁶⁶ located in the NBD promotes the localization of Hsp72 to the mitotic spindle and is required for efficient spindle assembly and chromosome congression and segregation. We determined the crystal structure of the Hsp72 NBD containing a genetically encoded phosphoserine at position 66. This revealed structural changes that stabilized interactions between subdomains within the NBD. ATP binding to the NBD o

SUBMITTER: Mukherjee M 

PROVIDER: S-EPMC6166782 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature