Structural Elements Directing G Proteins and β-Arrestin Interactions with the Human Melatonin Type 2 Receptor Revealed by Natural Variants.

ABSTRACT: G protein-coupled receptors (GPCRs) can engage distinct subsets of signaling pathways, but the structural determinants of this functional selectivity remain elusive. The naturally occurring genetic variants of GPCRs, selectively affecting different pathways, offer an opportunity to explore this phenomenon. We previously identified 40 coding variants of the MTNR1B gene encoding the melatonin MT₂ receptor (MT₂). These mutations differently impact the β-arrestin 2 recruitment, ERK activation, cAMP production, and Gα_i1 and Gα_z activation. In this study, we combined functional clustering and structural modeling to delineate the molecular features controlling the MT₂ functional selectivity. Using non-negative matrix factorization, we

SUBMITTER: Plouffe B 

PROVIDER: S-EPMC9281605 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature