GTP hydrolysis is modulated by Arg34 in the RASopathy-associated KRAS^P34R.

ABSTRACT: RAS proteins are commonly mutated in cancerous tumors, but germline RAS mutations are also found in RASopathy syndromes such as Noonan syndrome (NS) and cardiofaciocutaneous (CFC) syndrome. Activating RAS mutations can be subclassified based on their activating mechanisms. Understanding the structural basis for these mechanisms may provide clues for how to manage associated health conditions. We determined high-resolution X-ray structures of the RASopathy mutant KRAS^P34R seen in NS and CFCS. GTP and GDP-bound KRAS^P34R crystallized in multiple forms, with each lattice consisting of multiple protein conformations. In all GTP-bound conformations, the switch regions are not compatible with GAP binding, suggesting a structural mechanism for the GAP insensitivity of this RA

SUBMITTER: Bera AK 

PROVIDER: S-EPMC7495839 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature