Research ArticleG Protein Signaling

“Disruptor” residues in the regulator of G protein signaling (RGS) R12 subfamily attenuate the inactivation of Gα subunits

See allHide authors and affiliations

Sci. Signal.  12 Jun 2018:
Vol. 11, Issue 534, eaan3677
DOI: 10.1126/scisignal.aan3677

You are currently viewing the editor's summary.

View Full Text

Log in to view the full text

Log in through your institution

Log in through your institution

Designing specificity

Once an agonist binds to its G protein–coupled receptor, GTP replaces GDP on the α subunit of an associated G protein, which then dissociates from its βγ dimer to activate effectors. The GTPase activity of the α subunit returns the G protein to an inactive state, a process that is accelerated by interactions with members of the regulator of G protein signaling (RGS) family. Asli et al. used functional and structural analyses to identify specific amino acid residues that distinguished RGS proteins with low activity toward Gαo from those with high activity. High-activity RGS proteins that were mutated to contain these “disruptor” residues exhibited reduced inhibitory activity toward the Gα subunit. Together, these data suggest that “disruptor” residues within RGS proteins may encode specificity toward Gα subunits.