Exploiting conformational plasticity in the AAA+ protein VCP/p97 to modify function.

ABSTRACT: p97/VCP, a member of the AAA+ (ATPases associated with diverse cellular activities) family of proteins, is implicated in the etiology of a group of degenerative diseases affecting bone and muscle tissue as well as the central nervous system. Methyl-TROSY-based NMR studies have previously revealed how disease-causing mutations deregulate a subtle dynamic conformational equilibrium involving the N-terminal domain (NTD) with implications for the binding of certain adaptors, providing insight into how disease mutations lead to abnormal function. Herein the conformational plasticity of the p97 system is explored in an attempt to identify hotspots that can serve as targets for restoring function in disease mutants by shifting the position of the NTD back to its wild-type location. Although p97 i

SUBMITTER: Schutz AK 

PROVIDER: S-EPMC5565461 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature