Structural insights into the selective recognition of RF-amide peptides by neuropeptide FF receptor 2

ABSTRACT: Neuropeptide FF Receptor 2 (NPFFR2), a G protein-coupled receptor, plays a role in pain modulation and diet-induced thermogenesis. While NPFFR2 is strongly activated by neuropeptides FF (NPFFs), it shows low activity in response to RF-amide-related peptides (RFRPs), despite the peptides belonging to a shared family. In contrast, NPFFR1, which shares high sequence similarity with NPFFR2, is activated by RFRPs and regulates reproductive hormone balance. The molecular basis for these receptor-specific interactions with their RF-amide peptides remains unclear. Here, we present cryo-electron microscopy structures of NPFFR2 in its active state bound to the agonist RF-amide peptide hNPSF, and in its ligand-free state. Structural analysis reveals that the C-terminal RF-amide moiety engages conserv

SUBMITTER: Jeesoo Kim 

PROVIDER: S-SCDT-10_1038-S44319-025-00428-2 | biostudies-other |

REPOSITORIES: biostudies-other