Stachel-mediated activation of adhesion G protein-coupled receptors:insights from cryo-EM studies

摘要

Recently,a set of cryo-electron microscopy(cryo-EM)structures of different adhesion G protein-coupled receptors(aGPCRs)has been published by Xiao et al.1,Ping et al.2,Qu et al.3,and Barros-Álvarez et al.4 shedding light on the activation of the seven-helix transmembrane domain(7TMD)via their tethered peptide agonist.Adhesion GPCRs are an evolutionary old class of receptors that play a key role in several physiological processes including neuron and synapse formation,immune response,and metabolism.They are unique within the superfamily of GPCRs because they combine the structural features of adhesive molecules,mediating cell–cell or cell–matrix interaction,with intracellular G protein-mediated signalling.The long extracellular N terminus of the receptor harbours distinct functional domains including the highly conserved GPCR autoproteolysis-inducing(GAIN)domain with the GPCR proteolysis site(GPS).Many,but not all aGPCRs are autoproteolytically cleaved at the GPS into a N-and a C-terminal fragment(NTF and CTF,respectively),which remain non-covalently attached.