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基本情報
登録情報 | ![]() | |||||||||
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タイトル | Structure of the LM189-Bound beta2AR-Gi Complex | |||||||||
![]() | autosharpened map of lm189 bound b2gi complex | |||||||||
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![]() | GPCR / 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 / smooth muscle contraction / bone resorption / positive regulation of bone mineralization / potassium channel regulator activity / brown fat cell differentiation / intercellular bridge / positive regulation of protein localization to cell cortex / Adenylate cyclase inhibitory pathway / T cell migration / regulation of sodium ion transport / adenylate cyclase-activating adrenergic receptor signaling pathway / D2 dopamine receptor binding / response to prostaglandin E / G protein-coupled serotonin receptor binding / adenylate cyclase regulator activity / adenylate cyclase-inhibiting serotonin receptor signaling pathway / cellular response to forskolin / receptor-mediated endocytosis / regulation of mitotic spindle organization / response to cold / Regulation of insulin secretion / positive regulation of cholesterol biosynthetic process / G protein-coupled receptor binding / clathrin-coated endocytic vesicle membrane / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / response to peptide hormone / G-protein beta/gamma-subunit complex binding / centriolar satellite / Olfactory Signaling Pathway / 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 / 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 / Vasopressin regulates renal water homeostasis via Aquaporins / mitotic spindle / GDP binding / 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 / 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 / positive regulation of cold-induced thermogenesis / G protein activity / microtubule cytoskeleton / GTPase binding / Ca2+ pathway / retina development in camera-type eye / midbody 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: 2.9 Å | |||||||||
![]() | Casiraghi M / Wang H / Kobilka BK | |||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Structure and dynamics determine G protein coupling specificity at a class A GPCR. 著者: Marina Casiraghi / Haoqing Wang / Patrick C Brennan / Chris Habrian / Harald Hübner / Maximilian F Schmidt / Luis Maul / Biswaranjan Pani / Sherif M F M Bahriz / Bing Xu / Nico Staffen / ...著者: Marina Casiraghi / Haoqing Wang / Patrick C Brennan / Chris Habrian / Harald Hübner / Maximilian F Schmidt / Luis Maul / Biswaranjan Pani / Sherif M F M Bahriz / Bing Xu / Nico Staffen / Tufa E Assafa / Bohan Chen / Elizabeth White / Roger K Sunahara / Asuka Inoue / Yang K Xiang / Robert J Lefkowitz / Ehud Y Isacoff / Nathaniel Nucci / Peter Gmeiner / Michael T Lerch / Brian K Kobilka / ![]() ![]() ![]() 要旨: G protein-coupled receptors (GPCRs) exhibit varying degrees of selectivity for different G protein isoforms. Despite the abundant structures of GPCR-G protein complexes, little is known about the ...G protein-coupled receptors (GPCRs) exhibit varying degrees of selectivity for different G protein isoforms. Despite the abundant structures of GPCR-G protein complexes, little is known about the mechanism of G protein coupling specificity. The β-adrenergic receptor is an example of GPCR with high selectivity for Gαs, the stimulatory G protein for adenylyl cyclase, and much weaker for the Gαi family of G proteins inhibiting adenylyl cyclase. By developing a Gαi-biased agonist (LM189), we provide structural and biophysical evidence supporting that distinct conformations at ICL2 and TM6 are required for coupling of the different G protein subtypes Gαs and Gαi. These results deepen our understanding of G protein specificity and bias and can accelerate the design of ligands that select for preferred signaling pathways. | |||||||||
履歴 |
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構造の表示
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ダウンロードとリンク
-EMDBアーカイブ
マップデータ | ![]() | 56 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 21.8 KB 21.8 KB | 表示 表示 | ![]() |
画像 | ![]() | 78.4 KB | ||
Filedesc metadata | ![]() | 7.3 KB | ||
その他 | ![]() ![]() | 59.5 MB 59.5 MB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
関連構造データ | ![]() 9buyMC M: このマップから作成された原子モデル C: 同じ文献を引用 ( |
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類似構造データ | 類似検索 - 機能・相同性 ![]() |
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リンク
EMDBのページ | ![]() ![]() |
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「今月の分子」の関連する項目 |
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マップ
ファイル | ![]() | ||||||||||||||||||||||||||||||||||||
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注釈 | autosharpened map of lm189 bound b2gi 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: 1.111 Å | ||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
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-添付データ
-ハーフマップ: half map of lm189 bound b2gi complex
ファイル | emd_44925_half_map_1.map | ||||||||||||
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注釈 | half map of lm189 bound b2gi complex | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: half map of lm189 bound b2gi complex
ファイル | emd_44925_half_map_2.map | ||||||||||||
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注釈 | half map of lm189 bound b2gi complex | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
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試料の構成要素
-全体 : beta2 adrenergic receptor-Gi protein complex
全体 | 名称: beta2 adrenergic receptor-Gi protein complex |
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要素 |
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-超分子 #1: beta2 adrenergic receptor-Gi protein complex
超分子 | 名称: beta2 adrenergic receptor-Gi protein complex / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#5 |
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由来(天然) | 生物種: ![]() |
-分子 #1: Guanine nucleotide-binding protein G(i) subunit alpha-1
分子 | 名称: Guanine nucleotide-binding protein G(i) subunit alpha-1 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: 40.415031 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKSTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI ...文字列: MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKSTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI PTQQDVLRTR VKTTGIVETH FTFKDLHFKM FDVGGQRSER KKWIHCFEGV TAIIFCVALS DYDLVLAEDE EM NRMHESM KLFDSICNNK WFTDTSIILF LNKKDLFEEK IKKSPLTICY PEYAGSNTYE EAAAYIQCQF EDLNKRKDTK EIY THFTCA TDTKNVQFVF DAVTDVIIKN NLKDCGLF UniProtKB: Guanine nucleotide-binding protein G(i) subunit alpha-1 |
-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: 37.671102 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: PGSSGSELDQ LRQEAEQLKN QIRDARKACA DATLSQITNN IDPVGRIQMR TRRTLRGHLA KIYAMHWGTD SRLLVSASQD GKLIIWDSY TTNKVHAIPL RSSWVMTCAY APSGNYVACG GLDNICSIYN LKTREGNVRV SRELAGHTGY LSCCRFLDDN Q IVTSSGDT ...文字列: PGSSGSELDQ LRQEAEQLKN QIRDARKACA DATLSQITNN IDPVGRIQMR TRRTLRGHLA KIYAMHWGTD SRLLVSASQD GKLIIWDSY TTNKVHAIPL RSSWVMTCAY APSGNYVACG GLDNICSIYN LKTREGNVRV SRELAGHTGY LSCCRFLDDN Q IVTSSGDT TCALWDIETG QQTTTFTGHT GDVMSLSLAP DTRLFVSGAC DASAKLWDVR EGMCRQTFTG HESDINAICF FP NGNAFAT GSDDATCRLF DLRADQELMT YSHDNIICGI TSVSFSKSGR LLLAGYDDFN CNVWDALKAD RAGVLAGHDN RVS CLGVTD DGMAVATGSW DSFLKIWN 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: scFv16
分子 | 名称: scFv16 / タイプ: protein_or_peptide / ID: 4 / 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: 27.784896 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: DVQLVESGGG LVQPGGSRKL SCSASGFAFS SFGMHWVRQA PEKGLEWVAY ISSGSGTIYY ADTVKGRFTI SRDDPKNTLF LQMTSLRSE DTAMYYCVRS IYYYGSSPFD FWGQGTTLTV SSGGGGSGGG GSGGGGSDIV MTQATSSVPV TPGESVSISC R SSKSLLHS ...文字列: DVQLVESGGG LVQPGGSRKL SCSASGFAFS SFGMHWVRQA PEKGLEWVAY ISSGSGTIYY ADTVKGRFTI SRDDPKNTLF LQMTSLRSE DTAMYYCVRS IYYYGSSPFD FWGQGTTLTV SSGGGGSGGG GSGGGGSDIV MTQATSSVPV TPGESVSISC R SSKSLLHS NGNTYLYWFL QRPGQSPQLL IYRMSNLASG VPDRFSGSGS GTAFTLTISR LEAEDVGVYY CMQHLEYPLT FG AGTKLEL KAAAHHHHHH HH |
-分子 #5: Beta-2 adrenergic receptor
分子 | 名称: Beta-2 adrenergic receptor / 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: 51.767242 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MKTIIALSYI FCLVFADYKD DDDAMGQPGN GSAFLLAPNR SHAPDHDVEN LYFQGTQQRD EVWVVGMGIV MSLIVLAIVF GNVLVITAI AKFERLQTVT NYFITSLACA DLVMGLAVVP FGAAHILTKT WTFGNFWCEF WTSIDVLCVT ASIETLCVIA V DRYFAITS ...文字列: MKTIIALSYI FCLVFADYKD DDDAMGQPGN GSAFLLAPNR SHAPDHDVEN LYFQGTQQRD EVWVVGMGIV MSLIVLAIVF GNVLVITAI AKFERLQTVT NYFITSLACA DLVMGLAVVP FGAAHILTKT WTFGNFWCEF WTSIDVLCVT ASIETLCVIA V DRYFAITS PFKYQSLLTK NKARVIILMV WIVSGLTSFL PIQMHWYRAT HQEAINCYAE ETCCDFFTNQ AYAIASSIVS FY VPLVIMV FVYSRVFQEA KRQLQKIDKS EGRFHVQNLS QVEQDGRTGH GLRRSSKFCL KEHKALKTLG IIMGTFTLCW LPF FIVNIV HVIQDNLIRK EVYILLNWIG YVNSGFNPLI YCRSPDFRIA FQELLCLRRS SLKAYGNGYS SNGNTGEQSG LEVL FQGPY HVEQEKENKL LAEDLPGTED FVGHQGTVPS DNIDSQGRNA STNDSLLETS QVAPA UniProtKB: Beta-2 adrenergic receptor |
-分子 #6: CHOLESTEROL
分子 | 名称: CHOLESTEROL / タイプ: ligand / ID: 6 / コピー数: 3 / 式: CLR |
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分子量 | 理論値: 386.654 Da |
Chemical component information | ![]() ChemComp-CLR: |
-分子 #7: 4-[(1R)-1-hydroxy-2-{[6-(4-phenylbutoxy)hexyl]amino}ethyl]benzene...
分子 | 名称: 4-[(1R)-1-hydroxy-2-{[6-(4-phenylbutoxy)hexyl]amino}ethyl]benzene-1,2-diol タイプ: ligand / ID: 7 / コピー数: 1 / 式: A1ASM |
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分子量 | 理論値: 401.539 Da |
-分子 #8: N-[(3R)-4-(4-tert-butylphenyl)-3-({2-[(4-methoxyphenyl)sulfanyl]-...
分子 | 名称: N-[(3R)-4-(4-tert-butylphenyl)-3-({2-[(4-methoxyphenyl)sulfanyl]-5-[methyl(propan-2-yl)sulfamoyl]benzene-1-carbonyl}amino)butanoyl]glycine タイプ: ligand / ID: 8 / コピー数: 1 / 式: KBY |
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分子量 | 理論値: 669.851 Da |
Chemical component information | ![]() ChemComp-KBY: |
-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 |
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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 K3 BIOQUANTUM (6k x 4k) 平均電子線量: 52.5 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 / 最大 デフォーカス(公称値): 2.0 µm 最小 デフォーカス(公称値): 0.7000000000000001 µm |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |