Residue-level determinants of RGS R4 subfamily GAP activity and specificity towards the G_i subfamily.

ABSTRACT: The structural basis for the GTPase-accelerating activity of regulators of G protein signaling (RGS) proteins, as well as the mechanistic basis for their specificity in interacting with the heterotrimeric (αβγ) G proteins they inactivate, is not sufficiently understood at the family level. Here, we used biochemical assays to compare RGS domains across the RGS family and map those individual residues that favorably contribute to GTPase-accelerating activity, and those residues responsible for attenuating RGS domain interactions with Gα subunits. We show that conserved interactions of RGS residues with both the Gα switch I and II regions are crucial for RGS activity, while the reciprocal effects of "modulatory" and "disruptor" residues selectively modulate RGS activity. Our results quantify

SUBMITTER: Asli A 

PROVIDER: S-EPMC11072900 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature