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基本情報
登録情報 | データベース: EMDB / ID: EMD-9376 | |||||||||
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タイトル | B2V2R-Gs protein subcomplex of a GPCR-G protein-beta-arrestin mega-complex | |||||||||
![]() | B2V2R-Gs protein subcomplex of a GPCR-G protein-beta-arrestin mega-complex | |||||||||
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![]() | GPCR / Gs protein / signaling transducer / SIGNALING PROTEIN-IMMUNE SYSTEM complex | |||||||||
機能・相同性 | ![]() positive regulation of mini excitatory postsynaptic potential / beta2-adrenergic receptor activity / AMPA selective glutamate receptor signaling pathway / norepinephrine binding / positive regulation of autophagosome maturation / norepinephrine-epinephrine-mediated vasodilation involved in regulation of systemic arterial blood pressure / heat generation / Adrenoceptors / activation of transmembrane receptor protein tyrosine kinase activity / negative regulation of smooth muscle contraction ...positive regulation of mini excitatory postsynaptic potential / beta2-adrenergic receptor activity / AMPA selective glutamate receptor signaling pathway / norepinephrine binding / positive regulation of autophagosome maturation / norepinephrine-epinephrine-mediated vasodilation involved in regulation of systemic arterial blood pressure / heat generation / Adrenoceptors / activation of transmembrane receptor protein tyrosine kinase activity / negative regulation of smooth muscle contraction / positive regulation of lipophagy / negative regulation of G protein-coupled receptor signaling pathway / negative regulation of multicellular organism growth / adrenergic receptor signaling pathway / response to psychosocial stress / endosome to lysosome transport / diet induced thermogenesis / neuronal dense core vesicle / positive regulation of cAMP/PKA signal transduction / adenylate cyclase binding / PKA activation in glucagon signalling / smooth muscle contraction / hair follicle placode formation / developmental growth / D1 dopamine receptor binding / bone resorption / positive regulation of bone mineralization / potassium channel regulator activity / intracellular transport / vascular endothelial cell response to laminar fluid shear stress / brown fat cell differentiation / renal water homeostasis / intercellular bridge / Hedgehog 'off' state / viral release from host cell by cytolysis / regulation of sodium ion transport / adenylate cyclase-activating adrenergic receptor signaling pathway / activation of adenylate cyclase activity / peptidoglycan catabolic process / regulation of insulin secretion / cellular response to glucagon stimulus / receptor-mediated endocytosis / adenylate cyclase activator activity / response to cold / trans-Golgi network membrane / negative regulation of inflammatory response to antigenic stimulus / clathrin-coated endocytic vesicle membrane / bone development / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G-protein beta/gamma-subunit complex binding / platelet aggregation / Olfactory Signaling Pathway / cognition / Activation of the phototransduction cascade / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G protein-coupled acetylcholine receptor signaling pathway / adenylate cyclase-activating G protein-coupled receptor signaling pathway / G-protein activation / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through CDC42 / Glucagon signaling in metabolic regulation / cellular response to amyloid-beta / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / ADP signalling through P2Y purinoceptor 12 / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / cell wall macromolecule catabolic process / Vasopressin regulates renal water homeostasis via Aquaporins / mitotic spindle / G alpha (z) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / cellular response to catecholamine stimulus / ADORA2B mediated anti-inflammatory cytokines production / ADP signalling through P2Y purinoceptor 1 / G beta:gamma signalling through PI3Kgamma / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / adenylate cyclase-activating dopamine receptor signaling pathway / sensory perception of smell / lysozyme / lysozyme activity / GPER1 signaling / Inactivation, recovery and regulation of the phototransduction cascade / cellular response to prostaglandin E stimulus / G-protein beta-subunit binding / heterotrimeric G-protein complex / G alpha (12/13) signalling events / Cargo recognition for clathrin-mediated endocytosis / sensory perception of taste / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / Clathrin-mediated endocytosis / amyloid-beta binding 類似検索 - 分子機能 | |||||||||
生物種 | ![]() ![]() ![]() | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.8 Å | |||||||||
![]() | Nguyen AH / Thomsen ARB | |||||||||
資金援助 | ![]()
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![]() | ![]() 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 |
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構造の表示
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構造ビューア | EMマップ: ![]() ![]() ![]() |
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マップデータ | ![]() | 44.8 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 18.8 KB 18.8 KB | 表示 表示 | ![]() |
画像 | ![]() | 119.7 KB | ||
Filedesc metadata | ![]() | 6.8 KB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
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「今月の分子」の関連する項目 |
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ファイル | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | B2V2R-Gs protein subcomplex of a GPCR-G protein-beta-arrestin mega-complex | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
投影像・断面図 | 画像のコントロール
画像は Spider により作成 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.04 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
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-添付データ
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試料の構成要素
-全体 : B2V2R-Gs protein subcomplex of a GPCR-G protein-beta-arrestin meg...
全体 | 名称: B2V2R-Gs protein subcomplex of a GPCR-G protein-beta-arrestin mega-complex |
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要素 |
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-超分子 #1: B2V2R-Gs protein subcomplex of a GPCR-G protein-beta-arrestin meg...
超分子 | 名称: B2V2R-Gs protein subcomplex of a GPCR-G protein-beta-arrestin mega-complex タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#5 |
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-超分子 #2: B2V2R-Gs protein subcomplex
超分子 | 名称: B2V2R-Gs protein subcomplex / タイプ: complex / ID: 2 / 親要素: 1 / 含まれる分子: #1-#4 |
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由来(天然) | 生物種: ![]() |
-超分子 #3: Nanobody 35
超分子 | 名称: Nanobody 35 / タイプ: complex / ID: 3 / 親要素: 1 / 含まれる分子: #5 |
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由来(天然) | 生物種: ![]() ![]() |
-分子 #1: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
分子 | 名称: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short タイプ: protein_or_peptide / ID: 1 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 44.32616 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: MGCLGNSKTE DQRNEEKAQR EANKKIEKQL QKDKQVYRAT HRLLLLGAGE SGKSTIVKQM RILHVNGFNG DSEKATKVQD IKNNLKEAI ETIVAAMSNL VPPVELANPE NQFRVDYILS VMNVPDFDFP PEFYEHAKAL WEDEGVRACY ERSNEYQLID C AQYFLDKI ...文字列: MGCLGNSKTE DQRNEEKAQR EANKKIEKQL QKDKQVYRAT HRLLLLGAGE SGKSTIVKQM RILHVNGFNG DSEKATKVQD IKNNLKEAI ETIVAAMSNL VPPVELANPE NQFRVDYILS VMNVPDFDFP PEFYEHAKAL WEDEGVRACY ERSNEYQLID C AQYFLDKI DVIKQADYVP SDQDLLRCRV LTSGIFETKF QVDKVNFHMF DVGGQRDERR KWIQCFNDVT AIIFVVASSS YN MVIREDN QTNRLQEALN LFKSIWNNRW LRTISVILFL NKQDLLAEKV LAGKSKIEDY FPEFARYTTP EDATPEPGED PRV TRAKYF IRDEFLRIST ASGDGRHYCY PHFTCAVDTE NIRRVFNDCR DIIQRMHLRQ YELL UniProtKB: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short |
-分子 #2: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
分子 | 名称: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 タイプ: protein_or_peptide / ID: 2 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 38.534062 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: MHHHHHHGSS GSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKL IIWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC R FLDDNQIV ...文字列: MHHHHHHGSS GSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKL IIWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC R FLDDNQIV TSSGDTTCAL WDIETGQQTT TFTGHTGDVM SLSLAPDTRL FVSGACDASA KLWDVREGMC RQTFTGHESD IN AICFFPN GNAFATGSDD ATCRLFDLRA DQELMTYSHD NIICGITSVS FSKSGRLLLA GYDDFNCNVW DALKADRAGV LAG HDNRVS CLGVTDDGMA VATGSWDSFL KIWN UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 |
-分子 #3: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
分子 | 名称: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 タイプ: protein_or_peptide / ID: 3 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 7.861143 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFCAI L UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 |
-分子 #4: Endolysin,Beta-2 adrenergic receptor chimera
分子 | 名称: Endolysin,Beta-2 adrenergic receptor chimera / タイプ: protein_or_peptide / ID: 4 / コピー数: 1 / 光学異性体: LEVO / EC番号: lysozyme |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 57.630762 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MKTIIALSYI FCLVFADYKD DDDAENLYFQ GNIFEMLRID EGLRLKIYKD TEGYYTIGIG HLLTKSPSLN AAKSELDKAI GRNTNGVIT KDEAEKLFNQ DVDAAVRGIL RNAKLKPVYD SLDAVRRAAL INMVFQMGET GVAGFTNSLR MLQQKRWDEA A VNLAKSRW ...文字列: MKTIIALSYI FCLVFADYKD DDDAENLYFQ GNIFEMLRID EGLRLKIYKD TEGYYTIGIG HLLTKSPSLN AAKSELDKAI GRNTNGVIT KDEAEKLFNQ DVDAAVRGIL RNAKLKPVYD SLDAVRRAAL INMVFQMGET GVAGFTNSLR MLQQKRWDEA A VNLAKSRW YNQTPNRAKR VITTFRTGTW DAYAADEVWV VGMGIVMSLI VLAIVFGNVL VITAIAKFER LQTVTNYFIT SL ACADLVM GLAVVPFGAA HILTKTWTFG NFWCEFWTSI DVLCVTASIE TLCVIAVDRY FAITSPFKYQ SLLTKNKARV IIL MVWIVS GLTSFLPIQM HWYRATHQEA INCYAEETCC DFFTNQAYAI ASSIVSFYVP LVIMVFVYSR VFQEAKRQLQ KIDK SEGRF HVQNLSQVEQ DGRTGHGLRR SSKFCLKEHK ALKTLGIIMG TFTLCWLPFF IVNIVHVIQD NLIRKEVYIL LNWIG YVNS GFNPLIYCRS PDFRIAFQEL LC UniProtKB: Endolysin, Beta-2 adrenergic receptor |
-分子 #5: Nanobody 35
分子 | 名称: Nanobody 35 / タイプ: protein_or_peptide / ID: 5 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() ![]() |
分子量 | 理論値: 15.140742 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: QVQLQESGGG LVQPGGSLRL SCAASGFTFS NYKMNWVRQA PGKGLEWVSD ISQSGASISY TGSVKGRFTI SRDNAKNTLY LQMNSLKPE DTAVYYCARC PAPFTRDCFD VTSTTYAYRG QGTQVTVSSH HHHHHEPEA |
-分子 #6: 8-[(1R)-2-{[1,1-dimethyl-2-(2-methylphenyl)ethyl]amino}-1-hydroxy...
分子 | 名称: 8-[(1R)-2-{[1,1-dimethyl-2-(2-methylphenyl)ethyl]amino}-1-hydroxyethyl]-5-hydroxy-2H-1,4-benzoxazin-3(4H)-one タイプ: ligand / ID: 6 / コピー数: 1 / 式: P0G |
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分子量 | 理論値: 370.442 Da |
Chemical component information | ![]() ChemComp-P0G: |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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![]() | 単粒子再構成法 |
試料の集合状態 | particle |
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試料調製
緩衝液 | pH: 7.4 |
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グリッド | 詳細: unidentified |
凍結 | 凍結剤: ETHANE |
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電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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撮影 | フィルム・検出器のモデル: GATAN K2 QUANTUM (4k x 4k) 検出モード: SUPER-RESOLUTION / 平均電子線量: 104.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: ![]() |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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画像解析
初期モデル | モデルのタイプ: INSILICO MODEL |
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最終 再構成 | 想定した対称性 - 点群: C1 (非対称) / 解像度のタイプ: BY AUTHOR / 解像度: 3.8 Å / 解像度の算出法: FSC 0.143 CUT-OFF / ソフトウェア - 名称: cryoSPARC / 使用した粒子像数: 299893 |
初期 角度割当 | タイプ: OTHER / ソフトウェア - 名称: cryoSPARC |
最終 角度割当 | タイプ: OTHER / ソフトウェア - 名称: cryoSPARC |