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Structure paper

TitleStructural basis for Y2 receptor-mediated neuropeptide Y and peptide YY signaling.
Journal, issue, pagesStructure, Vol. 31, Issue 1, Page 44-57.e6, Year 2023
Publish dateJan 5, 2023
AuthorsHyunook Kang / Chaehee Park / Yeol Kyo Choi / Jungnam Bae / Sohee Kwon / Jinuk Kim / Chulwon Choi / Chaok Seok / Wonpil Im / Hee-Jung Choi /
PubMed AbstractNeuropeptide Y (NPY) and its receptors are expressed in various human tissues including the brain where they regulate appetite and emotion. Upon NPY stimulation, the neuropeptide Y1 and Y2 receptors ...Neuropeptide Y (NPY) and its receptors are expressed in various human tissues including the brain where they regulate appetite and emotion. Upon NPY stimulation, the neuropeptide Y1 and Y2 receptors (YR and YR, respectively) activate G signaling, but their physiological responses to food intake are different. In addition, deletion of the two N-terminal amino acids of peptide YY (PYY(3-36)), the endogenous form found in circulation, can stimulate YR but not YR, suggesting that YR and YR may have distinct ligand-binding modes. Here, we report the cryo-electron microscopy structures of the PYY(3-36)‒YR‒G and NPY‒YR‒G complexes. Using cell-based assays, molecular dynamics simulations, and structural analysis, we revealed the molecular basis of the exclusive binding of PYY(3-36) to YR. Furthermore, we demonstrated that YR favors G protein signaling over β-arrestin signaling upon activation, whereas YR does not show a preference between these two pathways.
External linksStructure / PubMed:36525977
MethodsEM (single particle)
Resolution2.89 - 3.39 Å
Structure data

33984

7yon

EMDB-33984, PDB-7yon:
Complex structure of Neuropeptide Y Y2 receptor in complex with PYY(3-36) and Gi
Method: EM (single particle) / Resolution: 2.95 Å

33985

7yoo

EMDB-33985, PDB-7yoo:
Complex structure of Neuropeptide Y Y2 receptor in complex with NPY and Gi
Method: EM (single particle) / Resolution: 3.11 Å

EMDB-35494: Complex structure of Neuropeptide Y Y2 receptor in complex with NPY and Gi (Consensus map)
Method: EM (single particle) / Resolution: 3.11 Å

EMDB-35495: Complex structure of Neuropeptide Y Y2 receptor in complex with NPY and Gi (Focused map on NPY-Y2R)
Method: EM (single particle) / Resolution: 3.39 Å

EMDB-35496: Complex structure of Neuropeptide Y Y2 receptor in complex with NPY and Gi (Focused map on Gi-scFv16)
Method: EM (single particle) / Resolution: 3.04 Å

EMDB-35497: Complex structure of Neuropeptide Y Y2 receptor in complex with PYY(3-36) and Gi (Consensus map)
Method: EM (single particle) / Resolution: 2.95 Å

EMDB-35498: Complex structure of Neuropeptide Y Y2 receptor in complex with PYY(3-36) and Gi (Focused map on PYY(3-36)-Y2R)
Method: EM (single particle) / Resolution: 3.15 Å

EMDB-35499: Complex structure of Neuropeptide Y Y2 receptor in complex with PYY(3-36) and Gi (Focused map on Gi-scFv16)
Method: EM (single particle) / Resolution: 2.89 Å

Chemicals

ChemComp-HOH:
WATER / Water

Source
  • homo sapiens (human)
  • mus musculus (house mouse)
KeywordsMEMBRANE PROTEIN / NPY / GPCR / G-protein / Complex / G-protein coupled receptor / neuropeptide y

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