+Search query
-Structure paper
Title | Structural basis for Y2 receptor-mediated neuropeptide Y and peptide YY signaling. |
---|---|
Journal, issue, pages | Structure, Vol. 31, Issue 1, Page 44-57.e6, Year 2023 |
Publish date | Jan 5, 2023 |
Authors | Hyunook Kang / Chaehee Park / Yeol Kyo Choi / Jungnam Bae / Sohee Kwon / Jinuk Kim / Chulwon Choi / Chaok Seok / Wonpil Im / Hee-Jung Choi / |
PubMed Abstract | 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 ...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 links | Structure / PubMed:36525977 |
Methods | EM (single particle) |
Resolution | 2.89 - 3.39 Å |
Structure data | EMDB-33984, PDB-7yon: EMDB-33985, PDB-7yoo: EMDB-35494: Complex structure of Neuropeptide Y Y2 receptor in complex with NPY and Gi (Consensus map) EMDB-35495: Complex structure of Neuropeptide Y Y2 receptor in complex with NPY and Gi (Focused map on NPY-Y2R) EMDB-35496: Complex structure of Neuropeptide Y Y2 receptor in complex with NPY and Gi (Focused map on Gi-scFv16) EMDB-35497: Complex structure of Neuropeptide Y Y2 receptor in complex with PYY(3-36) and Gi (Consensus map) EMDB-35498: Complex structure of Neuropeptide Y Y2 receptor in complex with PYY(3-36) and Gi (Focused map on PYY(3-36)-Y2R) EMDB-35499: Complex structure of Neuropeptide Y Y2 receptor in complex with PYY(3-36) and Gi (Focused map on Gi-scFv16) |
Chemicals | ChemComp-HOH: |
Source |
|
Keywords | MEMBRANE PROTEIN / NPY / GPCR / G-protein / Complex / G-protein coupled receptor / neuropeptide y |