Potent and Selective Peptide-based Inhibition of the G Protein Gαq.

ABSTRACT: In contrast to G protein-coupled receptors, for which chemical and peptidic inhibitors have been extensively explored, few compounds are available that directly modulate heterotrimeric G proteins. Active Gα_q binds its two major classes of effectors, the phospholipase C (PLC)-β isozymes and Rho guanine nucleotide exchange factors (RhoGEFs) related to Trio, in a strikingly similar fashion: a continuous helix-turn-helix of the effectors engages Gα_q within its canonical binding site consisting of a groove formed between switch II and helix α3. This information was exploited to synthesize peptides that bound active Gα_q in vitro with affinities similar to full-length effectors and directly competed with effectors for engagement of Gα_q A representative

SUBMITTER: Charpentier TH 

PROVIDER: S-EPMC5207258 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature