登録情報 データベース : PDB / ID : 6ni3 構造の表示 ダウンロードとリンクタイトル B2V2R-Gs protein subcomplex of a GPCR-G protein-beta-arrestin mega-complex 要素(Guanine nucleotide-binding protein ...) x 3 Endolysin,Beta-2 adrenergic receptor chimera Nanobody 35 詳細キーワード SIGNALING PROTEIN/IMMUNE SYSTEM / GPCR / Gs protein / signaling transducer / SIGNALING PROTEIN-IMMUNE SYSTEM complex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
: / beta2-adrenergic receptor activity / positive regulation of mini excitatory postsynaptic potential / positive regulation of cAMP-dependent protein kinase activity / norepinephrine binding / Adrenoceptors / heat generation / positive regulation of autophagosome maturation / positive regulation of AMPA receptor activity / norepinephrine-epinephrine-mediated vasodilation involved in regulation of systemic arterial blood pressure ... : / beta2-adrenergic receptor activity / positive regulation of mini excitatory postsynaptic potential / positive regulation of cAMP-dependent protein kinase activity / norepinephrine binding / Adrenoceptors / heat generation / positive regulation of autophagosome maturation / positive regulation of AMPA receptor activity / norepinephrine-epinephrine-mediated vasodilation involved in regulation of systemic arterial blood pressure / activation of transmembrane receptor protein tyrosine kinase activity / negative regulation of smooth muscle contraction / positive regulation of lipophagy / response to psychosocial stress / negative regulation of multicellular organism growth / adrenergic receptor signaling pathway / endosome to lysosome transport / diet induced thermogenesis / neuronal dense core vesicle / positive regulation of protein kinase A signaling / PKA activation in glucagon signalling / hair follicle placode formation / adenylate cyclase binding / smooth muscle contraction / mu-type opioid receptor binding / developmental growth / corticotropin-releasing hormone receptor 1 binding / potassium channel regulator activity / intracellular transport / D1 dopamine receptor binding / Hedgehog 'off' state / positive regulation of bone mineralization / brown fat cell differentiation / beta-2 adrenergic receptor binding / adenylate cyclase-activating adrenergic receptor signaling pathway / regulation of sodium ion transport / bone resorption / viral release from host cell by cytolysis / activation of adenylate cyclase activity / adenylate cyclase activator activity / response to cold / peptidoglycan catabolic process / receptor-mediated endocytosis / trans-Golgi network membrane / insulin-like growth factor receptor binding / ionotropic glutamate receptor binding / clathrin-coated endocytic vesicle membrane / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / bone development / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / positive regulation of protein serine/threonine kinase activity / G-protein activation / G protein-coupled acetylcholine receptor signaling pathway / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / adenylate cyclase-activating G protein-coupled receptor signaling pathway / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Sensory perception of sweet, bitter, and umami (glutamate) taste / cognition / photoreceptor disc membrane / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-type ligand receptors / Vasopressin regulates renal water homeostasis via Aquaporins / platelet aggregation / G alpha (z) signalling events / cellular response to catecholamine stimulus / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / adenylate cyclase-activating dopamine receptor signaling pathway / G beta:gamma signalling through PI3Kgamma / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / cellular response to amyloid-beta / GPER1 signaling / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / G alpha (12/13) signalling events / extracellular vesicle / sensory perception of smell / signaling receptor complex adaptor activity / cell wall macromolecule catabolic process / Thrombin signalling through proteinase activated receptors (PARs) / Cargo recognition for clathrin-mediated endocytosis / GTPase binding / lysozyme / retina development in camera-type eye / Clathrin-mediated endocytosis 類似検索 - 分子機能 Transducin (heterotrimeric G protein), gamma chain / G Protein Gi Gamma 2 / Beta 2 adrenoceptor / Adrenoceptor family / G-protein alpha subunit, group S / YVTN repeat-like/Quinoprotein amine dehydrogenase / Endolysin T4 type / T4-type lysozyme / Glycoside hydrolase, family 24 / Lysozyme domain superfamily ... Transducin (heterotrimeric G protein), gamma chain / G Protein Gi Gamma 2 / Beta 2 adrenoceptor / Adrenoceptor family / G-protein alpha subunit, group S / YVTN repeat-like/Quinoprotein amine dehydrogenase / Endolysin T4 type / T4-type lysozyme / Glycoside hydrolase, family 24 / Lysozyme domain superfamily / Phage lysozyme / 7 Propeller / Methylamine Dehydrogenase; Chain H / 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) / Few Secondary Structures / Irregular / Lysozyme-like domain superfamily / G-protein beta WD-40 repeat / P-loop containing nucleotide triphosphate hydrolases / 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 / Rossmann fold / 3-Layer(aba) Sandwich / Mainly Beta / Alpha Beta 類似検索 - ドメイン・相同性 Chem-P0G / Endolysin / Beta-2 adrenergic receptor / Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 / Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 / Guanine nucleotide-binding protein G(s) subunit alpha isoforms short 類似検索 - 構成要素生物種 Homo sapiens (ヒト) Enterobacteria phage RB59 (ファージ)Lama glama (ラマ)手法 電子顕微鏡法 / 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 3.8 Å 詳細データ登録者 Nguyen, A.H. / Thomsen, A.R.B. / Cahill, T.J. / des Georges, A. / Lefkowitz, R.J. 資金援助 米国, 2件 詳細 詳細を隠す組織 認可番号 国 Howard Hughes Medical Institute (HHMI) 米国 National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI) 2R01-HL016037-47 米国
引用ジャーナル : Nat Struct Mol Biol / 年 : 2019タイトル : Structure of an endosomal signaling GPCR-G protein-β-arrestin megacomplex.著者: Anthony H Nguyen / Alex R B Thomsen / Thomas J Cahill / Rick Huang / Li-Yin Huang / Tara Marcink / Oliver B Clarke / Søren Heissel / Ali Masoudi / Danya Ben-Hail / Fadi Samaan / Venkata P ... 著者 : Anthony H Nguyen / Alex R B Thomsen / Thomas J Cahill / Rick Huang / Li-Yin Huang / Tara Marcink / Oliver B Clarke / Søren Heissel / Ali Masoudi / Danya Ben-Hail / Fadi Samaan / Venkata P Dandey / Yong Zi Tan / Chuan Hong / Jacob P Mahoney / Sarah Triest / John Little / Xin Chen / Roger Sunahara / Jan Steyaert / Henrik Molina / Zhiheng Yu / Amedee des Georges / Robert J Lefkowitz / 要旨 : Classically, G-protein-coupled receptors (GPCRs) are thought to activate G protein from the plasma membrane and are subsequently desensitized by β-arrestin (β-arr). However, some GPCRs continue to ... Classically, G-protein-coupled receptors (GPCRs) are thought to activate G protein from the plasma membrane and are subsequently desensitized by β-arrestin (β-arr). However, some GPCRs continue to signal through G protein from internalized compartments, mediated by a GPCR-G protein-β-arr 'megaplex'. Nevertheless, the molecular architecture of the megaplex remains unknown. Here, we present its cryo-electron microscopy structure, which shows simultaneous engagement of human G protein and bovine β-arr to the core and phosphorylated tail, respectively, of a single active human chimeric β-adrenergic receptor with the C-terminal tail of the arginine vasopressin type 2 receptor (βVR). All three components adopt their canonical active conformations, suggesting that a single megaplex GPCR is capable of simultaneously activating G protein and β-arr. Our findings provide a structural basis for GPCR-mediated sustained internalized G protein signaling. 履歴 登録 2018年12月26日 登録サイト : RCSB / 処理サイト : RCSB改定 1.0 2019年11月20日 Provider : repository / タイプ : Initial release改定 1.1 2019年12月4日 Group : Database references / カテゴリ : citation / citation_authorItem : _citation.pdbx_database_id_PubMed / _citation.title / _citation_author.name改定 1.2 2019年12月18日 Group : Database references / カテゴリ : citation / citation_authorItem : _citation.journal_volume / _citation.page_first ... _citation.journal_volume / _citation.page_first / _citation.page_last / _citation_author.identifier_ORCID
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