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TitleMolecular mechanism of prolactin-releasing peptide recognition and signaling via its G protein-coupled receptor.
Journal, issue, pagesCell Discov, Vol. 10, Issue 1, Page 91, Year 2024
Publish dateSep 3, 2024
AuthorsYang Li / Qingning Yuan / Xinheng He / Yumu Zhang / Chongzhao You / Canrong Wu / Jingru Li / H Eric Xu / Li-Hua Zhao /
PubMed AbstractProlactin-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 ...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.
External linksCell Discov / PubMed:39223120 / PubMed Central
MethodsEM (single particle)
Resolution2.96 - 2.97 Å
Structure data

60353

8zps

EMDB-60353, PDB-8zps:
Cryo-EM structure of prolactin-releasing peptide recognition with Gi
Method: EM (single particle) / Resolution: 2.97 Å

60354

8zpt

EMDB-60354, PDB-8zpt:
Cryo-EM structure of prolactin-releasing peptide recognition with Gq
Method: EM (single particle) / Resolution: 2.96 Å

Source
  • homo sapiens (human)
KeywordsMEMBRANE PROTEIN / Melanin-Concentrating Hormone Receptors1 / GPCR

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