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基本情報
登録情報 | データベース: EMDB / ID: EMD-23996 | |||||||||
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タイトル | CryoEM Structure of mGlu2 - Gi Complex | |||||||||
![]() | Composite CryoEM Map of mGlu2 - Heterotrimeric Gi Complex | |||||||||
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機能・相同性 | ![]() regulation of response to drug / group II metabotropic glutamate receptor activity / behavioral response to nicotine / intracellular glutamate homeostasis / negative regulation of adenylate cyclase activity / G protein-coupled glutamate receptor signaling pathway / astrocyte projection / Class C/3 (Metabotropic glutamate/pheromone receptors) / glutamate secretion / glutamate receptor activity ...regulation of response to drug / group II metabotropic glutamate receptor activity / behavioral response to nicotine / intracellular glutamate homeostasis / negative regulation of adenylate cyclase activity / G protein-coupled glutamate receptor signaling pathway / astrocyte projection / Class C/3 (Metabotropic glutamate/pheromone receptors) / glutamate secretion / glutamate receptor activity / regulation of glutamate secretion / long-term synaptic depression / regulation of dopamine secretion / calcium channel regulator activity / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / regulation of cAMP-mediated signaling / D2 dopamine receptor binding / G protein-coupled serotonin receptor binding / regulation of mitotic spindle organization / cellular response to forskolin / regulation of synaptic transmission, glutamatergic / presynaptic modulation of chemical synaptic transmission / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / response to cocaine / Regulation of insulin secretion / G protein-coupled receptor activity / G protein-coupled receptor binding / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / 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 / 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 / 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 / response to peptide hormone / photoreceptor disc membrane / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-type ligand receptors / Vasopressin regulates renal water homeostasis via Aquaporins / 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 / GPER1 signaling / GDP binding / 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 / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / retina development in camera-type eye / presynaptic membrane / phospholipase C-activating G protein-coupled receptor signaling pathway / Ca2+ pathway / gene expression / cell cortex / midbody / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / scaffold protein binding / G alpha (q) signalling events / chemical synaptic transmission / cell population proliferation / Ras protein signal transduction / Extra-nuclear estrogen signaling / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / G protein-coupled receptor signaling pathway / cell cycle / cell division / lysosomal membrane / axon / GTPase activity / centrosome / glutamatergic synapse / synapse / dendrite / protein-containing complex binding / nucleolus 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: 3.2 Å | |||||||||
![]() | Seven AB / Barros-Alvarez X / Skiniotis G | |||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: G-protein activation by a metabotropic glutamate receptor. 著者: Alpay B Seven / Ximena Barros-Álvarez / Marine de Lapeyrière / Makaía M Papasergi-Scott / Michael J Robertson / Chensong Zhang / Robert M Nwokonko / Yang Gao / Justin G Meyerowitz / Jean- ...著者: Alpay B Seven / Ximena Barros-Álvarez / Marine de Lapeyrière / Makaía M Papasergi-Scott / Michael J Robertson / Chensong Zhang / Robert M Nwokonko / Yang Gao / Justin G Meyerowitz / Jean-Philippe Rocher / Dominik Schelshorn / Brian K Kobilka / Jesper M Mathiesen / Georgios Skiniotis / ![]() ![]() ![]() 要旨: Family C G-protein-coupled receptors (GPCRs) operate as obligate dimers with extracellular domains that recognize small ligands, leading to G-protein activation on the transmembrane (TM) domains of ...Family C G-protein-coupled receptors (GPCRs) operate as obligate dimers with extracellular domains that recognize small ligands, leading to G-protein activation on the transmembrane (TM) domains of these receptors by an unknown mechanism. Here we show structures of homodimers of the family C metabotropic glutamate receptor 2 (mGlu2) in distinct functional states and in complex with heterotrimeric G. Upon activation of the extracellular domain, the two transmembrane domains undergo extensive rearrangement in relative orientation to establish an asymmetric TM6-TM6 interface that promotes conformational changes in the cytoplasmic domain of one protomer. Nucleotide-bound G can be observed pre-coupled to inactive mGlu2, but its transition to the nucleotide-free form seems to depend on establishing the active-state TM6-TM6 interface. In contrast to family A and B GPCRs, G-protein coupling does not involve the cytoplasmic opening of TM6 but is facilitated through the coordination of intracellular loops 2 and 3, as well as a critical contribution from the C terminus of the receptor. The findings highlight the synergy of global and local conformational transitions to facilitate a new mode of G-protein activation. | |||||||||
履歴 |
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構造の表示
ムービー |
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構造ビューア | EMマップ: ![]() ![]() ![]() |
添付画像 |
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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 | ![]() | 4.6 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 24.9 KB 24.9 KB | 表示 表示 | ![]() |
画像 | ![]() | 97.4 KB | ||
その他 | ![]() ![]() ![]() ![]() | 2.9 MB 1 MB 2.2 MB 2.5 MB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-検証レポート
文書・要旨 | ![]() | 313.6 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 313.1 KB | 表示 | |
XML形式データ | ![]() | 7.4 KB | 表示 | |
CIF形式データ | ![]() | 8.5 KB | 表示 | |
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 | ![]() 7mtsMC ![]() 7mtqC ![]() 7mtrC 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 | |
電子顕微鏡画像生データ | ![]() Data #1: Unaligned multi-frame micrographs of mGlu2 - Gi Complex [micrographs - multiframe]) |
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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 | Composite CryoEM Map of mGlu2 - Heterotrimeric Gi Complex | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 0.8677 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
-追加マップ: Local and focused refinement of mGlu2 VFT and CRD domains
ファイル | emd_23996_additional_1.map | ||||||||||||
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注釈 | Local and focused refinement of mGlu2 VFT and CRD domains | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-追加マップ: Local and focused refinement of G-beta-gamma
ファイル | emd_23996_additional_2.map | ||||||||||||
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注釈 | Local and focused refinement of G-beta-gamma | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-追加マップ: Local and focused refinement of mGlu2 CRD and 7TM domains
ファイル | emd_23996_additional_3.map | ||||||||||||
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注釈 | Local and focused refinement of mGlu2 CRD and 7TM domains | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-追加マップ: Local and focused refinement of mGlu2 7TM domain and G-alpha-i
ファイル | emd_23996_additional_4.map | ||||||||||||
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注釈 | Local and focused refinement of mGlu2 7TM domain and G-alpha-i | ||||||||||||
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 : mGlu2 - Heterotrimeric Gi complex
全体 | 名称: mGlu2 - Heterotrimeric Gi complex |
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要素 |
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-超分子 #1: mGlu2 - Heterotrimeric Gi complex
超分子 | 名称: mGlu2 - Heterotrimeric Gi complex / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#4 詳細: Heterotrimeric G protein coupled metabotropic glutamate receptor 2 bound to Ago-PAM ADX55164 and L-Glutamate |
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由来(天然) | 生物種: ![]() |
組換発現 | 生物種: ![]() ![]() |
分子量 | 理論値: 277 KDa |
-分子 #1: Metabotropic glutamate receptor 2
分子 | 名称: Metabotropic glutamate receptor 2 / タイプ: protein_or_peptide / ID: 1 / コピー数: 2 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 93.932445 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: AEGPAKKVLT LEGDLVLGGL FPVHQKGGPA EDCGPVNEHR GIQRLEAMLF ALDRINRDPH LLPGVRLGAH ILDSCSKDTH ALEQALDFV RASLSRGADG SRHICPDGSY ATHGDAPTAI TGVIGGSYSD VSIQVANLLR LFQIPQISYA STSAKLSDKS R YDYFARTV ...文字列: AEGPAKKVLT LEGDLVLGGL FPVHQKGGPA EDCGPVNEHR GIQRLEAMLF ALDRINRDPH LLPGVRLGAH ILDSCSKDTH ALEQALDFV RASLSRGADG SRHICPDGSY ATHGDAPTAI TGVIGGSYSD VSIQVANLLR LFQIPQISYA STSAKLSDKS R YDYFARTV PPDFFQAKAM AEILRFFNWT YVSTVASEGD YGETGIEAFE LEARARNICV ATSEKVGRAM SRAAFEGVVR AL LQKPSAR VAVLFTRSED ARELLAASQR LNASFTWVAS DGWGALESVV AGSEGAAEGA ITIELASYPI SDFASYFQSL DPW NNSRNP WFREFWEQRF RCSFRQRDCA AHSLRAVPFE QESKIMFVVN AVYAMAHALH NMHRALCPNT TRLCDAMRPV NGRR LYKDF VLNVKFDAPF RPADTHNEVR FDRFGDGIGR YNIFTYLRAG SGRYRYQKVG YWAEGLTLDT SLIPWASPSA GPLPA SRCS EPCLQNEVKS VQPGEVCCWL CIPCQPYEYR LDEFTCADCG LGYWPNASLT GCFELPQEYI RWGDAWAVGP VTIACL GAL ATLFVLGVFV RHNATPVVKA SGRELCYILL GGVFLCYCMT FIFIAKPSTA VCTLRRLGLG TAFSVCYSAL LTKTNRI AR IFGGAREGAQ RPRFISPASQ VAICLALISG QLLIVVAWLV VEAPGTGKET APERREVVTL RCNHRDASML GSLAYNVL L IALCTLYAFK TRKCPENFNE AKFIGFTMYT TCIIWLAFLP IFYVTSSDYR VQTTTMCVSV SLSGSVVLGC LFAPKLHII LFQPQKNVVS HRAPTSRFGS AAARASSSLG QGSGSQFVPT VCNGREVVDS TTSSL |
-分子 #2: 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: 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: 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 |
-分子 #3: 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: 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: 37.342785 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: GSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKLI IWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC RFLDDNQIVT S SGDTTCAL ...文字列: GSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKLI IWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC RFLDDNQIVT S SGDTTCAL WDIETGQQTT TFTGHTGDVM SLSLAPDTRL FVSGACDASA KLWDVREGMC RQTFTGHESD INAICFFPNG NA FATGSDD ATCRLFDLRA DQELMTYSHD NIICGITSVS FSKSGRLLLA GYDDFNCNVW DALKADRAGV LAGHDNRVSC LGV TDDGMA VATGSWDSFL KIWN |
-分子 #4: 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: 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: 7.861143 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFCAI L |
-分子 #5: 2-methoxy-6-propyl-N-(2-{4-[(1H-tetrazol-5-yl)methoxy]phenyl}ethy...
分子 | 名称: 2-methoxy-6-propyl-N-(2-{4-[(1H-tetrazol-5-yl)methoxy]phenyl}ethyl)thieno[2,3-d]pyrimidin-4-amine タイプ: ligand / ID: 5 / コピー数: 1 / 式: ZQY |
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分子量 | 理論値: 425.507 Da |
Chemical component information | ![]() ChemComp-ZQY: |
-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: 2-acetamido-2-deoxy-beta-D-glucopyranose
分子 | 名称: 2-acetamido-2-deoxy-beta-D-glucopyranose / タイプ: ligand / ID: 7 / コピー数: 2 / 式: NAG |
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分子量 | 理論値: 221.208 Da |
Chemical component information | ![]() ChemComp-NAG: |
-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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グリッド | モデル: Quantifoil R1.2/1.3 / 支持フィルム - 材質: GOLD / 支持フィルム - トポロジー: HOLEY |
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) 検出モード: COUNTING / 平均電子線量: 1.3 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: ![]() |
電子光学系 | C2レンズ絞り径: 50.0 µm / 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD / Cs: 2.7 mm / 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): 1.0 µm |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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画像解析
最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 3.2 Å / 解像度の算出法: FSC 0.143 CUT-OFF / ソフトウェア - 名称: cryoSPARC (ver. 3.2) / 詳細: A composite map of four locally refined maps. / 使用した粒子像数: 799323 |
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初期 角度割当 | タイプ: OTHER |
最終 角度割当 | タイプ: OTHER |