The molecular basis for immune dysregulation by the hyperactivated E62K mutant of the GTPase RAC2.

ABSTRACT: The RAS-related C3 botulinum toxin substrate 2 (RAC2) is a member of the RHO subclass of RAS superfamily GTPases required for proper immune function. An activating mutation in a key switch II region of RAC2 (RAC2^E62K) involved in recognizing modulatory factors and effectors has been identified in patients with common variable immune deficiency. To better understand how the mutation dysregulates RAC2 function, we evaluated the structure and stability, guanine nucleotide exchange factor (GEF) and GTPase-activating protein (GAP) activity, and effector binding of RAC2^E62K Our findings indicate the E62K mutation does not alter RAC2 structure or stability. However, it does alter GEF specificity, as RAC2^E62K is activated by the DOCK GEF, DOCK2, but not by the Dbl

SUBMITTER: Arrington ME 

PROVIDER: S-EPMC7443499 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature