Identification of Key Regions Mediating Human Melatonin Type 1 Receptor Functional Selectivity Revealed by Natural Variants.

ABSTRACT: Melatonin is a hormone mainly produced by the pineal gland and MT₁ is one of the two G protein-coupled receptors (GPCRs) mediating its action. Despite an increasing number of available GPCR crystal structures, the molecular mechanism of activation of a large number of receptors, including MT₁, remains poorly understood. The purpose of this study is to elucidate the structural elements involved in the process of MT₁'s activation using naturally occurring variants affecting its function. Thirty-six nonsynonymous variants, including 34 rare ones, were identified in MTNR1A (encoding MT₁) from a cohort of 8687 individuals and their signaling profiles were characterized using Bioluminescence Resonance Energy Transfer-based sensors probing 11 dif

SUBMITTER: Hegron A 

PROVIDER: S-EPMC8507577 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature