7YON

Complex structure of Neuropeptide Y Y2 receptor in complex with PYY(3-36) and Gi

7YON の概要

• エントリーDOI: 10.2210/pdb7yon/pdb
• 関連するPDBエントリー: 7YOO
• EMDBエントリー: 33984 35497 35498 35499
• 分子名称: Guanine nucleotide-binding protein G(i) subunit alpha-1, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2, ... (7 entities in total)
• 機能のキーワード: npy, gpcr, g-protein, complex, membrane protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 161627.81

構造登録者

Kang, H.,Park, C.,Kim, J.,Choi, H.-J. (登録日: 2022-08-01, 公開日: 2023-03-22)

主引用文献

Kang, H.,Park, C.,Choi, Y.K.,Bae, J.,Kwon, S.,Kim, J.,Choi, C.,Seok, C.,Im, W.,Choi, H.J.
Structural basis for Y2 receptor-mediated neuropeptide Y and peptide YY signaling.
Structure, 31:44-57.e6, 2023

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 (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.

PubMed: 36525977
DOI: 10.1016/j.str.2022.11.010

実験手法

ELECTRON MICROSCOPY (2.95 Å)