- EMDB-36476: Focused refinement structure of GRK2 in NTSR1-GRK2-Galpha(q) complexes -
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基本情報
登録情報
データベース: EMDB / ID: EMD-36476
タイトル
Focused refinement structure of GRK2 in NTSR1-GRK2-Galpha(q) complexes
マップデータ
試料
複合体: Focused refinement structure of GRK2 in NTSR1-GRK2-Galpha(q) complexes
タンパク質・ペプチド: Beta-adrenergic receptor kinase 1
リガンド: STAUROSPORINE
キーワード
Biased signaling / SIGNALING PROTEIN
機能・相同性
機能・相同性情報
Calmodulin induced events / beta-adrenergic-receptor kinase / negative regulation of the force of heart contraction by chemical signal / negative regulation of relaxation of smooth muscle / Activation of SMO / beta-adrenergic receptor kinase activity / G protein-coupled receptor kinase activity / Edg-2 lysophosphatidic acid receptor binding / alpha-2A adrenergic receptor binding / negative regulation of striated muscle contraction ...Calmodulin induced events / beta-adrenergic-receptor kinase / negative regulation of the force of heart contraction by chemical signal / negative regulation of relaxation of smooth muscle / Activation of SMO / beta-adrenergic receptor kinase activity / G protein-coupled receptor kinase activity / Edg-2 lysophosphatidic acid receptor binding / alpha-2A adrenergic receptor binding / negative regulation of striated muscle contraction / desensitization of G protein-coupled receptor signaling pathway / Cargo recognition for clathrin-mediated endocytosis / positive regulation of protein localization to cilium / regulation of the force of heart contraction / G protein-coupled receptor internalization / positive regulation of smoothened signaling pathway / G alpha (s) signalling events / G alpha (q) signalling events / regulation of signal transduction / cardiac muscle contraction / cell projection / G protein-coupled receptor binding / intracellular protein transport / G protein-coupled acetylcholine receptor signaling pathway / presynapse / peptidyl-serine phosphorylation / postsynapse / protein kinase activity / G protein-coupled receptor signaling pathway / protein phosphorylation / ATP binding / membrane / plasma membrane / cytosol / cytoplasm 類似検索 - 分子機能
GPCR kinase / Regulator of G protein signaling domain / RGS, subdomain 2 / RGS domain / RGS domain profile. / Regulator of G protein signalling domain / RGS domain superfamily / Extension to Ser/Thr-type protein kinases / AGC-kinase, C-terminal / AGC-kinase C-terminal domain profile. ...GPCR kinase / Regulator of G protein signaling domain / RGS, subdomain 2 / RGS domain / RGS domain profile. / Regulator of G protein signalling domain / RGS domain superfamily / Extension to Ser/Thr-type protein kinases / AGC-kinase, C-terminal / AGC-kinase C-terminal domain profile. / PH domain / PH domain profile. / Pleckstrin homology domain. / Pleckstrin homology domain / PH-like domain superfamily / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / Protein kinase domain / Serine/Threonine protein kinases, catalytic domain / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily 類似検索 - ドメイン・相同性
National Natural Science Foundation of China (NSFC)
中国
引用
ジャーナル: Nature / 年: 2023 タイトル: GPCR activation and GRK2 assembly by a biased intracellular agonist. 著者: Jia Duan / Heng Liu / Fenghui Zhao / Qingning Yuan / Yujie Ji / Xiaoqing Cai / Xinheng He / Xinzhu Li / Junrui Li / Kai Wu / Tianyu Gao / Shengnan Zhu / Shi Lin / Ming-Wei Wang / Xi Cheng / ...著者: Jia Duan / Heng Liu / Fenghui Zhao / Qingning Yuan / Yujie Ji / Xiaoqing Cai / Xinheng He / Xinzhu Li / Junrui Li / Kai Wu / Tianyu Gao / Shengnan Zhu / Shi Lin / Ming-Wei Wang / Xi Cheng / Wanchao Yin / Yi Jiang / Dehua Yang / H Eric Xu / 要旨: Phosphorylation of G-protein-coupled receptors (GPCRs) by GPCR kinases (GRKs) desensitizes G-protein signalling and promotes arrestin signalling, which is also modulated by biased ligands. The ...Phosphorylation of G-protein-coupled receptors (GPCRs) by GPCR kinases (GRKs) desensitizes G-protein signalling and promotes arrestin signalling, which is also modulated by biased ligands. The molecular assembly of GRKs on GPCRs and the basis of GRK-mediated biased signalling remain largely unknown owing to the weak GPCR-GRK interactions. Here we report the complex structure of neurotensin receptor 1 (NTSR1) bound to GRK2, Gα and the arrestin-biased ligand SBI-553. The density map reveals the arrangement of the intact GRK2 with the receptor, with the N-terminal helix of GRK2 docking into the open cytoplasmic pocket formed by the outward movement of the receptor transmembrane helix 6, analogous to the binding of the G protein to the receptor. SBI-553 binds at the interface between GRK2 and NTSR1 to enhance GRK2 binding. The binding mode of SBI-553 is compatible with arrestin binding but clashes with the binding of Gα protein, thus providing a mechanism for its arrestin-biased signalling capability. In sum, our structure provides a rational model for understanding the details of GPCR-GRK interactions and GRK2-mediated biased signalling.