Structural basis of adhesion GPCR GPR110 activation by stalk peptide and G-proteins coupling.

ABSTRACT: Adhesion G protein-coupled receptors (aGPCRs) are keys of many physiological events and attractive targets for various diseases. aGPCRs are also known to be capable of self-activation via an autoproteolysis process that removes the inhibitory GAIN domain on the extracellular side of receptor and releases a stalk peptide to bind and activate the transmembrane side of receptor. However, the detailed mechanism of aGPCR activation remains elusive. Here, we report the cryo-electron microscopy structures of GPR110 (ADGRF1), a member of aGPCR, in complex with G_q, G_s, G_i, G₁₂ and G_13. The structures reveal distinctive ligand engaging model and activation conformations of GPR110. The structures also unveil the rarely explored GPCR/G₁₂

SUBMITTER: Zhu X 

PROVIDER: S-EPMC9489763 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature