ジャーナル: Structure / 年: 2023 タイトル: Structural basis for Y2 receptor-mediated neuropeptide Y and peptide YY signaling. 著者: Hyunook Kang / Chaehee Park / Yeol Kyo Choi / Jungnam Bae / Sohee Kwon / Jinuk Kim / Chulwon Choi / Chaok Seok / Wonpil Im / Hee-Jung Choi / 要旨: 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.
フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) 平均電子線量: 66.0 e/Å2
実験機器
モデル: Titan Krios / 画像提供: FEI Company
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画像解析
粒子像選択
選択した数: 9842630
初期モデル
#0 - モデルのタイプ: OTHER #0 - 詳細: Initial 3D volume generated by ab initio reconstruction #1 - モデルのタイプ: OTHER #1 - 詳細: Initial 3D volume generated by ab initio reconstruction
初期 角度割当
タイプ: MAXIMUM LIKELIHOOD / ソフトウェア - 名称: cryoSPARC (ver. 3.2)
最終 角度割当
タイプ: MAXIMUM LIKELIHOOD / ソフトウェア - 名称: cryoSPARC (ver. 3.2)