An inactive receptor-G protein complex maintains the dynamic range of agonist-induced signaling.

ABSTRACT: Agonist binding promotes activation of G protein-coupled receptors (GPCRs) and association of active receptors with G protein heterotrimers. The resulting active-state ternary complex is the basis for conventional stimulus-response coupling. Although GPCRs can also associate with G proteins before agonist binding, the impact of such preassociated complexes on agonist-induced signaling is poorly understood. Here we show that preassociation of 5-HT₇ serotonin receptors with G_s heterotrimers is necessary for agonist-induced signaling. 5-HT₇ receptors in their inactive state associate with G_s, as these complexes are stabilized by inverse agonists and receptor mutations that favor the inactive state. Inactive-state 5-HT₇-G_s compl

SUBMITTER: Jang W 

PROVIDER: S-EPMC7720138 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature