EMD-60353
Cryo-EM structure of prolactin-releasing peptide recognition with Gi
EMD-60353
Single-particle2.97 Å
![EMD-60353](https://www.ebi.ac.uk/emdb/images/entry/EMD-60353/400_60353.gif)
Map released: 25/09/2024
Last modified: 20/11/2024
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
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
![](http://www.ebi.ac.uk/web_guidelines/images/logos/orcid/orcid_16x16.png)
![](http://www.ebi.ac.uk/web_guidelines/images/logos/orcid/orcid_16x16.png)
![](http://www.ebi.ac.uk/web_guidelines/images/logos/orcid/orcid_16x16.png)
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 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.
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.