EMD-60353

Single-particle
2.97 Å
EMD-60353 Deposition: 31/05/2024
Map released: 25/09/2024
Last modified: 20/11/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-60353

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

EMD-60353

Single-particle
2.97 Å
EMD-60353 Deposition: 31/05/2024
Map released: 25/09/2024
Last modified: 20/11/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Homo sapiens
Sample: Molecular mechanism of prolactin-releasing peptide recognition with Gi
Fitted models: 8zps (Avg. Q-score: 0.406)

Deposition Authors: Zhao L, Li Y, Yuan Q, Xu HE , Shan H, Hu W, Wu K, Xu HE , Zhang Y, Wu C, Wu K, Shen J, Xu HE
Molecular mechanism of prolactin-releasing peptide recognition and signaling via its G protein-coupled receptor.
Li Y, Yuan Q, He X, Zhang Y, You C , Wu C, Li J, Xu HE , Zhao LH
(2024) Cell Discov , 10 , 91 - 91
PUBMED: 39223120
DOI: doi:10.1038/s41421-024-00724-6
ISSN: 2056-5968
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 Gq or Gi 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.