8ZPS

Cryo-EM structure of prolactin-releasing peptide recognition with Gi

Summary for 8ZPS

• Entry DOI: 10.2210/pdb8zps/pdb
• EMDB information: 60353
• Descriptor: Guanine nucleotide-binding protein G(s) subunit alpha-1, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, SCFV16, ... (6 entities in total)
• Functional Keywords: melanin-concentrating hormone receptors1, gpcr, membrane protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 6
• Total formula weight: 159313.55

Authors

Zhao, L.,Li, Y.,Yuan, Q.,Xu, H.E. (deposition date: 2024-05-31, release date: 2024-09-25)

Primary citation

Li, Y.,Yuan, Q.,He, X.,Zhang, Y.,You, C.,Wu, C.,Li, J.,Xu, H.E.,Zhao, L.H.
Molecular mechanism of prolactin-releasing peptide recognition and signaling via its G protein-coupled receptor.
Cell Discov, 10:91-91, 2024

PubMed 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 or G 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. Structural comparison with neuropeptide Y receptors reveals both similarities and differences in engaging the essential RF/RY-amide motifs. Our findings demonstrate the general mechanism governing RF-amide motif recognition by PrRPR and RF-amide peptide receptors, and provide a foundation for elucidating activation mechanisms and developing selective drugs targeting this important peptide-receptor system.

PubMed: 39223120
DOI: 10.1038/s41421-024-00724-6

Experimental method

ELECTRON MICROSCOPY (2.97 Å)