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TitleReceptor-specific recognition of NPY peptides revealed by structures of NPY receptors.
Journal, issue, pagesSci Adv, Vol. 8, Issue 18, Page eabm1232, Year 2022
Publish dateMay 6, 2022
AuthorsTingting Tang / Qiuxiang Tan / Shuo Han / Anne Diemar / Kristin Löbner / Hongyu Wang / Corinna Schüß / Victoria Behr / Karin Mörl / Mu Wang / Xiaojing Chu / Cuiying Yi / Max Keller / Jacob Kofoed / Steffen Reedtz-Runge / Anette Kaiser / Annette G Beck-Sickinger / Qiang Zhao / Beili Wu /
PubMed AbstractIn response to three highly conserved neuropeptides, neuropeptide Y (NPY), peptide YY, and pancreatic polypeptide (PP), four G protein-coupled receptors mediate multiple essential physiological ...In response to three highly conserved neuropeptides, neuropeptide Y (NPY), peptide YY, and pancreatic polypeptide (PP), four G protein-coupled receptors mediate multiple essential physiological processes, such as food intake, vasoconstriction, sedation, and memory retention. Here, we report the structures of the human Y, Y, and Y receptors in complex with NPY or PP, and the G protein. These structures reveal distinct binding poses of the peptide upon coupling to different receptors, reflecting the importance of the conformational plasticity of the peptide in recognizing the NPY receptors. The N terminus of the peptide forms extensive interactions with the Y receptor, but not with the Y and Y receptors. Supported by mutagenesis and functional studies, subtype-specific interactions between the receptors and peptides were further observed. These findings provide insight into key factors that govern NPY signal recognition and transduction, and would enable development of selective drugs.
External linksSci Adv / PubMed:35507650 / PubMed Central
MethodsEM (single particle)
Resolution3.0 - 3.4 Å
Structure data

EMDB-33069, PDB-7x9a:
Cryo-EM structure of neuropeptide Y Y1 receptor in complex with NPY and Gi
Method: EM (single particle) / Resolution: 3.2 Å

EMDB-33070, PDB-7x9b:
Cryo-EM structure of neuropeptide Y Y2 receptor in complex with NPY and Gi
Method: EM (single particle) / Resolution: 3.4 Å

EMDB-33071, PDB-7x9c:
Cryo-EM structure of neuropeptide Y Y4 receptor in complex with PP and Gi
Method: EM (single particle) / Resolution: 3.0 Å

Source
  • homo sapiens (human)
KeywordsSIGNALING PROTEIN / pancreatic polypeptide / Gi protein

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