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基本情報
登録情報 | ![]() | |||||||||
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タイトル | mGlu2-4 heterodimer bound with Gi | |||||||||
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![]() | GPCR / MEMBRANE PROTEIN | |||||||||
機能・相同性 | ![]() adenylate cyclase-inhibiting G protein-coupled glutamate receptor signaling pathway / regulation of response to drug / group II metabotropic glutamate receptor activity / adenylate cyclase inhibiting G protein-coupled glutamate receptor activity / intracellular glutamate homeostasis / behavioral response to nicotine / negative regulation of adenylate cyclase activity / G protein-coupled glutamate receptor signaling pathway / astrocyte projection / neurotransmitter secretion ...adenylate cyclase-inhibiting G protein-coupled glutamate receptor signaling pathway / regulation of response to drug / group II metabotropic glutamate receptor activity / adenylate cyclase inhibiting G protein-coupled glutamate receptor activity / intracellular glutamate homeostasis / behavioral response to nicotine / negative regulation of adenylate cyclase activity / G protein-coupled glutamate receptor signaling pathway / astrocyte projection / neurotransmitter secretion / Class C/3 (Metabotropic glutamate/pheromone receptors) / glutamate receptor activity / glutamate secretion / GTP metabolic process / long-term synaptic depression / regulation of glutamate secretion / cellular response to stress / regulation of dopamine secretion / positive regulation of macroautophagy / Adenylate cyclase inhibitory pathway / regulation of synaptic transmission, glutamatergic / regulation of neuron apoptotic process / presynaptic modulation of chemical synaptic transmission / calcium channel regulator activity / response to cocaine / G protein-coupled receptor binding / G protein-coupled receptor activity / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / 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 / 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 / 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 / sensory perception of taste / extracellular vesicle / presynapse / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / presynaptic membrane / GTPase binding / retina development in camera-type eye / Ca2+ pathway / midbody / cytoplasmic vesicle / fibroblast proliferation / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / scaffold protein binding / G alpha (i) signalling events / G alpha (s) signalling events / phospholipase C-activating G protein-coupled receptor signaling pathway / chemical synaptic transmission / G alpha (q) signalling events / gene expression / Ras protein signal transduction / postsynaptic membrane / Extra-nuclear estrogen signaling / cell population proliferation / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / positive regulation of MAPK cascade / ciliary basal body / G protein-coupled receptor signaling pathway / axon / lysosomal membrane / cell division / GTPase activity / synapse / dendrite 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: 3.7 Å | |||||||||
![]() | Zhang Y / Liu J | |||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Structural basis of orientated asymmetry in a mGlu heterodimer. 著者: Weizhu Huang / Nan Jin / Jia Guo / Cangsong Shen / Chanjuan Xu / Kun Xi / Léo Bonhomme / Robert B Quast / Dan-Dan Shen / Jiao Qin / Yi-Ru Liu / Yuxuan Song / Yang Gao / Emmanuel Margeat / ...著者: Weizhu Huang / Nan Jin / Jia Guo / Cangsong Shen / Chanjuan Xu / Kun Xi / Léo Bonhomme / Robert B Quast / Dan-Dan Shen / Jiao Qin / Yi-Ru Liu / Yuxuan Song / Yang Gao / Emmanuel Margeat / Philippe Rondard / Jean-Philippe Pin / Yan Zhang / Jianfeng Liu / ![]() ![]() 要旨: The structural basis for the allosteric interactions within G protein-coupled receptors (GPCRs) heterodimers remains largely unknown. The metabotropic glutamate (mGlu) receptors are complex dimeric ...The structural basis for the allosteric interactions within G protein-coupled receptors (GPCRs) heterodimers remains largely unknown. The metabotropic glutamate (mGlu) receptors are complex dimeric GPCRs important for the fine tuning of many synapses. Heterodimeric mGlu receptors with specific allosteric properties have been identified in the brain. Here we report four cryo-electron microscopy structures of mGlu2-4 heterodimer in different states: an inactive state bound to antagonists, two intermediate states bound to either mGlu2 or mGlu4 agonist only and an active state bound to both glutamate and a mGlu4 positive allosteric modulator (PAM) in complex with Gi protein. In addition to revealing a unique PAM binding pocket among mGlu receptors, our data bring important information for the asymmetric activation of mGlu heterodimers. First, we show that agonist binding to a single subunit in the extracellular domain is not sufficient to stabilize an active dimer conformation. Single-molecule FRET data show that the monoliganded mGlu2-4 can be found in both intermediate states and an active one. Second, we provide a detailed view of the asymmetric interface in seven-transmembrane (7TM) domains and identified key residues within the mGlu2 7TM that limits its activation leaving mGlu4 as the only subunit activating G proteins. | |||||||||
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-検証レポート
文書・要旨 | ![]() | 350.2 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 349.8 KB | 表示 | |
XML形式データ | ![]() | 6.9 KB | 表示 | |
CIF形式データ | ![]() | 8 KB | 表示 | |
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-関連構造データ
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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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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: 0.93 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
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試料の構成要素
-全体 : mGlu2-mGlu4 heterodimer bound Gi
全体 | 名称: mGlu2-mGlu4 heterodimer bound Gi |
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要素 |
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-超分子 #1: mGlu2-mGlu4 heterodimer bound Gi
超分子 | 名称: mGlu2-mGlu4 heterodimer bound Gi / 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)/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: 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: 37.285734 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: SELDQLRQEA EQLKNQIRDA RKACADATLS QITNNIDPVG RIQMRTRRTL RGHLAKIYAM HWGTDSRLLV SASQDGKLII WDSYTTNKV HAIPLRSSWV MTCAYAPSGN YVACGGLDNI CSIYNLKTRE GNVRVSRELA GHTGYLSCCR FLDDNQIVTS S GDTTCALW ...文字列: SELDQLRQEA EQLKNQIRDA RKACADATLS QITNNIDPVG RIQMRTRRTL RGHLAKIYAM HWGTDSRLLV SASQDGKLII WDSYTTNKV HAIPLRSSWV MTCAYAPSGN YVACGGLDNI CSIYNLKTRE GNVRVSRELA GHTGYLSCCR FLDDNQIVTS S GDTTCALW DIETGQQTTT FTGHTGDVMS LSLAPDTRLF VSGACDASAK LWDVREGMCR QTFTGHESDI NAICFFPNGN AF ATGSDDA TCRLFDLRAD QELMTYSHDN IICGITSVSF SKSGRLLLAG YDDFNCNVWD ALKADRAGVL AGHDNRVSCL GVT DDGMAV ATGSWDSFLK IWN UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 |
-分子 #2: 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: 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: 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 #3: Metabotropic glutamate receptor 2
分子 | 名称: Metabotropic glutamate receptor 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: 93.861367 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: EGPAKKVLTL EGDLVLGGLF PVHQKGGPAE DCGPVNEHRG IQRLEAMLFA LDRINRDPHL LPGVRLGAHI LDSCSKDTHA LEQALDFVR ASLSRGADGS RHICPDGSYA THGDAPTAIT GVIGGSYSDV SIQVANLLRL FQIPQISYAS TSAKLSDKSR Y DYFARTVP ...文字列: EGPAKKVLTL EGDLVLGGLF PVHQKGGPAE DCGPVNEHRG IQRLEAMLFA LDRINRDPHL LPGVRLGAHI LDSCSKDTHA LEQALDFVR ASLSRGADGS RHICPDGSYA THGDAPTAIT GVIGGSYSDV SIQVANLLRL FQIPQISYAS TSAKLSDKSR Y DYFARTVP PDFFQAKAMA EILRFFNWTY VSTVASEGDY GETGIEAFEL EARARNICVA TSEKVGRAMS RAAFEGVVRA LL QKPSARV AVLFTRSEDA RELLAASQRL NASFTWVASD GWGALESVVA GSEGAAEGAI TIELASYPIS DFASYFQSLD PWN NSRNPW FREFWEQRFR CSFRQRDCAA HSLRAVPFEQ ESKIMFVVNA VYAMAHALHN MHRALCPNTT RLCDAMRPVN GRRL YKDFV LNVKFDAPFR PADTHNEVRF DRFGDGIGRY NIFTYLRAGS GRYRYQKVGY WAEGLTLDTS LIPWASPSAG PLPAS RCSE PCLQNEVKSV QPGEVCCWLC IPCQPYEYRL DEFTCADCGL GYWPNASLTG CFELPQEYIR WGDAWAVGPV TIACLG ALA TLFVLGVFVR HNATPVVKAS GRELCYILLG GVFLCYCMTF IFIAKPSTAV CTLRRLGLGT AFSVCYSALL TKTNRIA RI FGGAREGAQR PRFISPASQV AICLALISGQ LLIVVAWLVV EAPGTGKETA PERREVVTLR CNHRDASMLG SLAYNVLL I ALCTLYAFKT RKCPENFNEA KFIGFTMYTT CIIWLAFLPI FYVTSSDYRV QTTTMCVSVS LSGSVVLGCL FAPKLHIIL FQPQKNVVSH RAPTSRFGSA AARASSSLGQ GSGSQFVPTV CNGREVVDST TSSL UniProtKB: Metabotropic glutamate receptor 2 |
-分子 #4: Guanine nucleotide-binding protein G(i) subunit alpha-3
分子 | 名称: Guanine nucleotide-binding protein G(i) subunit alpha-3 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: 40.584156 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MGCTLSAEDK AAVERSKMID RNLREDGEKA AKEVKLLLLG AGESGKNTIV KQMKIIHEDG YSEDECKQYK VVVYSNTIQS IIAIIRAMG RLKIDFGEAA RADDARQLFV LAGSAEEGVM TPELAGVIKR LWRDGGVQAC FSRSREYQLN DSASYYLNDL D RISQSNYI ...文字列: MGCTLSAEDK AAVERSKMID RNLREDGEKA AKEVKLLLLG AGESGKNTIV KQMKIIHEDG YSEDECKQYK VVVYSNTIQS IIAIIRAMG RLKIDFGEAA RADDARQLFV LAGSAEEGVM TPELAGVIKR LWRDGGVQAC FSRSREYQLN DSASYYLNDL D RISQSNYI PTQQDVLRTR VKTTGIVETH FTFKDLYFKM FDVGAQRSER KKWIHCFEGV TAIIFCVALS DYDLVLAEDE EM NRMHASM KLFDSICNNK WFTETSIILF LNKKDLFEEK IKRSPLTICY PEYTGSNTYE EAAAYIQCQF EDLNRRKDTK EIY THFTCS TDTKNVQFVF DAVTDVIIKN NLKECGLY UniProtKB: Guanine nucleotide-binding protein G(i) subunit alpha-3 |
-分子 #5: Metabotropic glutamate receptor 4
分子 | 名称: Metabotropic glutamate receptor 4 / 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: 98.36532 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: KPKGHPHMNS IRIDGDITLG GLFPVHGRGS EGKPCGELKK EKGIHRLEAM LFALDRINND PDLLPNITLG ARILDTCSRD THALEQSLT FVQALIEKDG TEVRCGSGGP PIITKPERVV GVIGASGSSV SIMVANILRL FKIPQISYAS TAPDLSDNSR Y DFFSRVVP ...文字列: KPKGHPHMNS IRIDGDITLG GLFPVHGRGS EGKPCGELKK EKGIHRLEAM LFALDRINND PDLLPNITLG ARILDTCSRD THALEQSLT FVQALIEKDG TEVRCGSGGP PIITKPERVV GVIGASGSSV SIMVANILRL FKIPQISYAS TAPDLSDNSR Y DFFSRVVP SDTYQAQAMV DIVRALKWNY VSTVASEGSY GESGVEAFIQ KSREDGGVCI AQSVKIPREP KAGEFDKIIR RL LETSNAR AVIIFANEDD IRRVLEAARR ANQTGHFFWM GSDSWGSKIA PVLHLEEVAE GAVTILPKRM SVRGFDRYFS SRT LDNNRR NIWFAEFWED NFHCKLSRHA LKKGSHVKKC TNRERIGQDS AYEQEGKVQF VIDAVYAMGH ALHAMHRDLC PGRV GLCPR MDPVDGTQLL KYIRNVNFSG IAGNPVTFNE NGDAPGRYDI YQYQLRNDSA EYKVIGSWTD HLHLRIERMH WPGSG QQLP RSICSLPCQP GERKKTVKGM PCCWHCEPCT GYQYQVDRYT CKTCPYDMRP TENRTGCRPI PIIKLEWGSP WAVLPL FLA VVGIAATLFV VITFVRYNDT PIVKASGREL SYVLLAGIFL CYATTFLMIA EPDLGTCSLR RIFLGLGMSI SYAALLT KT NRIYRIFEQG KRSVSAPRFI SPASQLAITF SLISLQLLGI CVWFVVDPSH SVVDFQDQRT LDPRFARGVL KCDISDLS L ICLLGYSMLL MVTCTVYAIK TRGVPETFNE AKPIGFTMYT TCIVWLAFIP IFFGTSQSAD KLYIQTTTLT VSVSLSASV SLGMLYMPKV YIILFHPEQN VPKRKRSLKA VVTAATMSNK FTQKGNFRPN GEAKSELCEN LEAPALATKQ TYVTYTNHAI UniProtKB: Metabotropic glutamate receptor 4 |
-分子 #6: GLUTAMIC ACID
分子 | 名称: GLUTAMIC ACID / タイプ: ligand / ID: 6 / コピー数: 2 / 式: GLU |
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分子量 | 理論値: 147.129 Da |
Chemical component information | ![]() ChemComp-GLU: |
-分子 #7: (1R,2S)-2-[[3,5-bis(chloranyl)phenyl]carbamoyl]cyclohexane-1-carb...
分子 | 名称: (1R,2S)-2-[[3,5-bis(chloranyl)phenyl]carbamoyl]cyclohexane-1-carboxylic acid タイプ: ligand / ID: 7 / コピー数: 1 / 式: W9R |
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分子量 | 理論値: 316.18 Da |
-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: 7.5 |
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凍結 | 凍結剤: ETHANE |
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電子顕微鏡法
顕微鏡 | TFS KRIOS |
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撮影 | フィルム・検出器のモデル: FEI FALCON IV (4k x 4k) 平均電子線量: 52.0 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 / 最大 デフォーカス(公称値): 3.0 µm / 最小 デフォーカス(公称値): 0.6 µm |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |