Molecular basis for allosteric agonism and G protein subtype selectivity of galanin receptors.

ABSTRACT: Peptide hormones and neuropeptides are complex signaling molecules that predominately function through G protein-coupled receptors (GPCRs). Two unanswered questions remaining in the field of peptide-GPCR signaling systems pertain to the basis for the diverse binding modes of peptide ligands and the specificity of G protein coupling. Here, we report the structures of a neuropeptide, galanin, bound to its receptors, GAL1R and GAL2R, in complex with their primary G protein subtypes G_i and G_q, respectively. The structures reveal a unique binding pose of galanin, which almost 'lays flat' on the top of the receptor transmembrane domain pocket in an α-helical conformation, and acts as an 'allosteric-like' agonist via a distinct signal transduction cascade. The structures als

SUBMITTER: Duan J 

PROVIDER: S-EPMC8924211 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature