Molecular mechanism of prolactin-releasing peptide recognition and signaling via its G protein-coupled receptor.

ABSTRACT: Prolactin-releasing peptide (PrRP) is an RF-amide neuropeptide that binds and activates its cognate G protein-coupled receptor, prolactin-releasing peptide receptor (PrRPR), also known as GPR10. PrRP and PrRPR are highly conserved across mammals and involved in regulating a range of physiological processes, including stress response, appetite regulation, pain modulation, cardiovascular function, and potentially reproductive functions. Here we present cryo-electron microscopy structures of PrRP-bound PrRPR coupled to G_q or G_i heterotrimer, unveiling distinct molecular determinants underlying the specific recognition of the ligand's C-terminal RF-amide motif. We identify a conserved polar pocket that accommodates the C-terminal amide shared by RF-amide peptides. Structu

SUBMITTER: Li Y 

PROVIDER: S-EPMC11369081 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature