登録情報 データベース : EMDB / ID : EMD-36474 ダウンロードとリンクタイトル cryo-EM structure of NTSR1-GRK2-Galpha(q) complexes 1 マップデータ 詳細 試料複合体 : NTSR1-GRK2-Galpha(q) complexes 1タンパク質・ペプチド : Beta-adrenergic receptor kinase 1タンパク質・ペプチド : NTS(8-13)タンパク質・ペプチド : Guanine nucleotide-binding protein G(q) subunit alphaタンパク質・ペプチド : Neurotensin receptor type 1リガンド : STAUROSPORINEリガンド : GUANOSINE-5'-DIPHOSPHATEリガンド : MAGNESIUM IONリガンド : TETRAFLUOROALUMINATE IONリガンド : 2-[{2-(1-fluorocyclopropyl)-4-[4-(2-methoxyphenyl)piperidin-1-yl]quinazolin-6-yl}(methyl)amino]ethan-1-ol 残り2件を表示 表示を減らす 詳細 キーワード Biased signaling / SIGNALING PROTEIN機能・相同性 機能・相同性情報分子機能 ドメイン・相同性 構成要素
Calmodulin induced events / negative regulation of the force of heart contraction by chemical signal / negative regulation of relaxation of smooth muscle / beta-adrenergic-receptor kinase / Activation of SMO / beta-adrenergic receptor kinase activity / G protein-coupled neurotensin receptor activity / G protein-coupled receptor kinase activity / Edg-2 lysophosphatidic acid receptor binding / alpha-2A adrenergic receptor binding ... Calmodulin induced events / negative regulation of the force of heart contraction by chemical signal / negative regulation of relaxation of smooth muscle / beta-adrenergic-receptor kinase / Activation of SMO / beta-adrenergic receptor kinase activity / G protein-coupled neurotensin receptor activity / G protein-coupled receptor kinase activity / Edg-2 lysophosphatidic acid receptor binding / alpha-2A adrenergic receptor binding / inositol phosphate catabolic process / tachykinin receptor signaling pathway / symmetric synapse / Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion / Acetylcholine regulates insulin secretion / phospholipase C-activating G protein-coupled glutamate receptor signaling pathway / negative regulation of striated muscle contraction / D-aspartate import across plasma membrane / positive regulation of gamma-aminobutyric acid secretion / positive regulation of protein localization to cilium / Cargo recognition for clathrin-mediated endocytosis / phospholipase C-activating serotonin receptor signaling pathway / PLC beta mediated events / desensitization of G protein-coupled receptor signaling pathway / regulation of membrane depolarization / cytoplasmic side of mitochondrial outer membrane / entrainment of circadian clock / regulation of platelet activation / positive regulation of arachidonate secretion / regulation of the force of heart contraction / L-glutamate import across plasma membrane / regulation of respiratory gaseous exchange / positive regulation of inhibitory postsynaptic potential / positive regulation of smoothened signaling pathway / G protein-coupled receptor internalization / negative regulation of systemic arterial blood pressure / positive regulation of glutamate secretion / negative regulation of release of sequestered calcium ion into cytosol / regulation of canonical Wnt signaling pathway / G alpha (s) signalling events / glutamate receptor signaling pathway / G alpha (q) signalling events / positive regulation of inositol phosphate biosynthetic process / response to lipid / temperature homeostasis / detection of temperature stimulus involved in sensory perception of pain / phototransduction, visible light / postsynaptic cytosol / photoreceptor outer segment / neuropeptide signaling pathway / regulation of signal transduction / cardiac muscle contraction / enzyme regulator activity / response to prostaglandin E / GTPase activator activity / viral genome replication / positive regulation of release of sequestered calcium ion into cytosol / dendritic shaft / Peptide ligand-binding receptors / adult locomotory behavior / learning / Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells / negative regulation of protein kinase activity / cell projection / intracellular protein transport / G protein-coupled receptor binding / terminal bouton / G protein-coupled receptor activity / G-protein beta/gamma-subunit complex binding / cytoplasmic side of plasma membrane / Thromboxane signalling through TP receptor / G protein-coupled acetylcholine receptor signaling pathway / adenylate cyclase-activating G protein-coupled receptor signaling pathway / G-protein activation / blood coagulation / ADP signalling through P2Y purinoceptor 1 / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / heterotrimeric G-protein complex / presynapse / Thrombin signalling through proteinase activated receptors (PARs) / peptidyl-serine phosphorylation / G protein activity / heart development / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / 加水分解酵素; 酸無水物に作用; GTPに作用・細胞または細胞小器官の運動に関与 / phospholipase C-activating G protein-coupled receptor signaling pathway / chemical synaptic transmission / nuclear membrane / G alpha (q) signalling events / dendritic spine / perikaryon / postsynapse / protein kinase activity / protein stabilization / protein phosphorylation / G protein-coupled receptor signaling pathway / positive regulation of apoptotic process / membrane raft / symbiont entry into host cell / lysosomal membrane 類似検索 - 分子機能 Neurotensin receptor / Neurotensin type 1 receptor / GPCR kinase / G-protein alpha subunit, group Q / Regulator of G protein signaling domain / RGS domain / RGS domain profile. / Regulator of G protein signalling domain / RGS, subdomain 2 / RGS domain superfamily ... Neurotensin receptor / Neurotensin type 1 receptor / GPCR kinase / G-protein alpha subunit, group Q / Regulator of G protein signaling domain / RGS domain / RGS domain profile. / Regulator of G protein signalling domain / RGS, subdomain 2 / 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 / Guanine nucleotide binding protein (G-protein), alpha subunit / G protein alpha subunit, helical insertion / G-protein alpha subunit / G-alpha domain profile. / G protein alpha subunit / G-protein coupled receptors family 1 signature. / G protein-coupled receptor, rhodopsin-like / GPCR, rhodopsin-like, 7TM / G-protein coupled receptors family 1 profile. / 7 transmembrane receptor (rhodopsin family) / 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 / P-loop containing nucleoside triphosphate hydrolase 類似検索 - ドメイン・相同性 Beta-adrenergic receptor kinase 1 / Neurotensin receptor type 1 / Guanine nucleotide-binding protein G(q) subunit alpha 類似検索 - 構成要素生物種 Homo sapiens (ヒト) / Bos taurus (ウシ) / synthetic construct (人工物) 手法 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 3.07 Å 詳細 データ登録者Duan J / Liu H / Zhao F / Yuan Q / Ji Y / Xu HE 資金援助 中国, 1件 詳細 詳細を隠すOrganization Grant number 国 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. 履歴 登録 2023年6月11日 - ヘッダ(付随情報) 公開 2023年8月9日 - マップ公開 2023年8月9日 - 更新 2023年8月30日 - 現状 2023年8月30日 処理サイト : PDBj / 状態 : 公開
すべて表示 表示を減らす