Positive allosteric modulation of a GPCR ternary complex.

ABSTRACT: The activation of a G protein-coupled receptor (GPCR) leads to the formation of a ternary complex between agonist, receptor, and G protein that is characterized by high-affinity binding. Allosteric modulators bind to a distinct binding site from the orthosteric agonist and can modulate both the affinity and the efficacy of orthosteric agonists. The influence allosteric modulators have on the high-affinity active state of the GPCR-G protein ternary complex is unknown due to limitations on attempting to characterize this interaction in recombinant whole cell or membrane-based assays. Here, we use the purified M₂ muscarinic acetylcholine receptor reconstituted into nanodiscs to show that, once the agonist-bound high-affinity state is promoted by the G protein, positive allosteric m

SUBMITTER: Burger WAC 

PROVIDER: S-EPMC11389776 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature