Structural basis of tethered agonism of the adhesion GPCRs ADGRD1 and ADGRF1.

ABSTRACT: Adhesion G protein-coupled receptors (aGPCRs) are essential for a variety of physiological processes such as immune responses, organ development, cellular communication, proliferation and homeostasis^1-7. An intrinsic manner of activation that involves a tethered agonist in the N-terminal region of the receptor has been proposed for the aGPCRs^8,9, but its molecular mechanism remains elusive. Here we report the G protein-bound structures of ADGRD1 and ADGRF1, which exhibit many unique features with regard to the tethered agonism. The stalk region that proceeds the first transmembrane helix acts as the tethered agonist by forming extensive interactions with the transmembrane domain; these interactions are mostly conserved in ADGRD1 and ADGRF1, suggesting that a common st

SUBMITTER: Qu X 

PROVIDER: S-EPMC9046087 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature