登録情報 データベース : EMDB / ID : EMD-22357 構造の表示 ダウンロードとリンクタイトル Structural Basis of the Activation of Heterotrimeric Gs-protein by Isoproterenol-bound Beta1-Adrenergic Receptor マップデータActivation of Heterotrimeric Gs-protein by Isoproterenol-bound Beta1-Adrenergic Receptor 詳細 試料複合体 : Isoproterenol bound beta1 adrenergic receptor in complex with heterotrimeric Gs protein複合体 : 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タンパク質・ペプチド : Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1タンパク質・ペプチド : Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2複合体 : Nanobody 35複合体 : Guanine nucleotide-binding protein G(s) subunit alpha isoforms shortタンパク質・ペプチド : Guanine nucleotide-binding protein G(s) subunit alpha isoforms short複合体 : Beta1-Adrenergic Receptorタンパク質・ペプチド : Beta1-Adrenergic Receptorリガンド : ISOPRENALINE 詳細機能・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
beta1-adrenergic receptor activity / positive regulation of heart rate by epinephrine-norepinephrine / Olfactory Signaling Pathway / Sensory perception of sweet, bitter, and umami (glutamate) taste / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / regulation of circadian sleep/wake cycle, sleep / sensory perception of chemical stimulus / Activation of the phototransduction cascade / Activation of G protein gated Potassium channels / G-protein activation ... beta1-adrenergic receptor activity / positive regulation of heart rate by epinephrine-norepinephrine / Olfactory Signaling Pathway / Sensory perception of sweet, bitter, and umami (glutamate) taste / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / regulation of circadian sleep/wake cycle, sleep / sensory perception of chemical stimulus / Activation of the phototransduction cascade / Activation of G protein gated Potassium channels / G-protein activation / G beta:gamma signalling through PI3Kgamma / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through PLC beta / ADP signalling through P2Y purinoceptor 1 / Thromboxane signalling through TP receptor / Presynaptic function of Kainate receptors / G beta:gamma signalling through CDC42 / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / G alpha (12/13) signalling events / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / norepinephrine-epinephrine-mediated vasodilation involved in regulation of systemic arterial blood pressure / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Thrombin signalling through proteinase activated receptors (PARs) / Ca2+ pathway / G alpha (z) signalling events / Extra-nuclear estrogen signaling / G alpha (s) signalling events / G alpha (q) signalling events / G alpha (i) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / mu-type opioid receptor binding / corticotropin-releasing hormone receptor 1 binding / D1 dopamine receptor binding / beta-2 adrenergic receptor binding / adenylate cyclase-activating adrenergic receptor signaling pathway / adenylate cyclase activator activity / ionotropic glutamate receptor binding / insulin-like growth factor receptor binding / G-protein beta/gamma-subunit complex binding / adenylate cyclase-activating G protein-coupled receptor signaling pathway / photoreceptor disc membrane / cellular response to catecholamine stimulus / adenylate cyclase-activating dopamine receptor signaling pathway / cellular response to prostaglandin E stimulus / G-protein beta-subunit binding / heterotrimeric G-protein complex / signaling receptor complex adaptor activity / early endosome / G protein-coupled receptor signaling pathway / GTPase activity / GTP binding / identical protein binding / membrane / metal ion binding / plasma membrane / cytoplasm 類似検索 - 分子機能 Beta 1 adrenoceptor / Adrenoceptor family / G-protein alpha subunit, group S / Serpentine type 7TM GPCR chemoreceptor Srsx / G-alpha domain profile. / Guanine nucleotide binding protein (G-protein), alpha subunit / G protein alpha subunit, helical insertion / G-protein alpha subunit / G protein alpha subunit / G-protein, gamma subunit ... Beta 1 adrenoceptor / Adrenoceptor family / G-protein alpha subunit, group S / Serpentine type 7TM GPCR chemoreceptor Srsx / G-alpha domain profile. / Guanine nucleotide binding protein (G-protein), alpha subunit / G protein alpha subunit, helical insertion / G-protein alpha subunit / G protein alpha subunit / G-protein, gamma subunit / G-protein gamma subunit domain profile. / GGL domain / G-protein gamma-like domain superfamily / G-protein gamma-like domain / GGL domain / G protein gamma subunit-like motifs / Guanine nucleotide-binding protein, beta subunit / G-protein, beta 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) / G-protein beta WD-40 repeat / WD40 repeat, conserved site / Trp-Asp (WD) repeats signature. / Trp-Asp (WD) repeats profile. / Trp-Asp (WD) repeats circular profile. / WD domain, G-beta repeat / WD40 repeats / WD40 repeat / WD40-repeat-containing domain superfamily / WD40/YVTN repeat-like-containing domain superfamily / P-loop containing nucleoside triphosphate hydrolase 類似検索 - ドメイン・相同性 Guanine nucleotide-binding protein G(s) subunit alpha isoforms short / Beta-1 adrenergic receptor / 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 類似検索 - 構成要素生物種 Bos taurus (ウシ) / Lama glama (ラマ) / Meleagris gallopavo (シチメンチョウ)手法 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 2.6 Å 詳細 データ登録者Su M / Zhu L / Zhang Y / Paknejad N / Dey R / Huang J / Lee MY / Williams D / Jordan KD / Eng ET ...Su M / Zhu L / Zhang Y / Paknejad N / Dey R / Huang J / Lee MY / Williams D / Jordan KD / Eng ET / Ernst OP / Meyerson JR / Hite RK / Walz T / Liu W / Huang XY 資金援助 米国, 1件 詳細 詳細を隠すOrganization Grant number 国 National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI) HL130478 米国
引用ジャーナル : Mol Cell / 年 : 2020タイトル : Structural Basis of the Activation of Heterotrimeric Gs-Protein by Isoproterenol-Bound β-Adrenergic Receptor.著者: Minfei Su / Lan Zhu / Yixiao Zhang / Navid Paknejad / Raja Dey / Jianyun Huang / Ming-Yue Lee / Dewight Williams / Kelsey D Jordan / Edward T Eng / Oliver P Ernst / Joel R Meyerson / Richard ... 著者 : Minfei Su / Lan Zhu / Yixiao Zhang / Navid Paknejad / Raja Dey / Jianyun Huang / Ming-Yue Lee / Dewight Williams / Kelsey D Jordan / Edward T Eng / Oliver P Ernst / Joel R Meyerson / Richard K Hite / Thomas Walz / Wei Liu / Xin-Yun Huang / 要旨 : Cardiac disease remains the leading cause of morbidity and mortality worldwide. The β-adrenergic receptor (β-AR) is a major regulator of cardiac functions and is downregulated in the majority of ... Cardiac disease remains the leading cause of morbidity and mortality worldwide. The β-adrenergic receptor (β-AR) is a major regulator of cardiac functions and is downregulated in the majority of heart failure cases. A key physiological process is the activation of heterotrimeric G-protein Gs by β-ARs, leading to increased heart rate and contractility. Here, we use cryo-electron microscopy and functional studies to investigate the molecular mechanism by which β-AR activates Gs. We find that the tilting of α5-helix breaks a hydrogen bond between the sidechain of His373 in the C-terminal α5-helix and the backbone carbonyl of Arg38 in the N-terminal αN-helix of Gα. Together with the disruption of another interacting network involving Gln59 in the α1-helix, Ala352 in the β6-α5 loop, and Thr355 in the α5-helix, these conformational changes might lead to the deformation of the GDP-binding pocket. Our data provide molecular insights into the activation of G-proteins by G-protein-coupled receptors. 履歴 登録 2020年7月27日 - ヘッダ(付随情報) 公開 2020年9月2日 - マップ公開 2020年9月2日 - 更新 2020年10月14日 - 現状 2020年10月14日 処理サイト : RCSB / 状態 : 公開
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