+ データを開く
データを開く
- 基本情報
基本情報
| 登録情報 | データベース: EMDB / ID: EMD-31031 | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| タイトル | Cryo-EM structure of Gi-bound metabotropic glutamate receptor mGlu2 | ||||||||||||||||||
|  マップデータ | |||||||||||||||||||
|  試料 | 
 | ||||||||||||||||||
|  キーワード | mGlu2 / GPCR / Cryo-EM / complex / MEMBRANE PROTEIN | ||||||||||||||||||
| 機能・相同性 |  機能・相同性情報 regulation of response to drug / group II metabotropic glutamate receptor activity / intracellular glutamate homeostasis / behavioral response to nicotine / negative regulation of adenylate cyclase activity / G protein-coupled glutamate receptor signaling pathway / Class C/3 (Metabotropic glutamate/pheromone receptors) / glutamate receptor activity / glutamate secretion / long-term synaptic depression ...regulation of response to drug / group II metabotropic glutamate receptor activity / intracellular glutamate homeostasis / behavioral response to nicotine / negative regulation of adenylate cyclase activity / G protein-coupled glutamate receptor signaling pathway / Class C/3 (Metabotropic glutamate/pheromone receptors) / glutamate receptor activity / glutamate secretion / long-term synaptic depression / regulation of glutamate secretion / astrocyte projection / cellular response to stress / regulation of dopamine secretion / regulation of synaptic transmission, glutamatergic / adenylate cyclase inhibitor activity / positive regulation of protein localization to cell cortex / Adenylate cyclase inhibitory pathway / T cell migration / D2 dopamine receptor binding / response to prostaglandin E / adenylate cyclase regulator activity / G protein-coupled serotonin receptor binding / adenylate cyclase-inhibiting serotonin receptor signaling pathway / presynaptic modulation of chemical synaptic transmission / cellular response to forskolin / regulation of mitotic spindle organization / response to cocaine / calcium channel regulator activity / Regulation of insulin secretion / positive regulation of cholesterol biosynthetic process / negative regulation of insulin secretion / G protein-coupled receptor binding / G protein-coupled receptor activity / response to peptide hormone / 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 / Activation of G protein gated Potassium channels / Inhibition  of voltage gated Ca2+ channels via Gbeta/gamma subunits / G-protein activation / 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 / photoreceptor disc membrane / Sensory perception of sweet, bitter, and umami (glutamate) taste / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / GDP binding / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / G alpha (z) signalling events / cellular response to catecholamine stimulus / ADP signalling through P2Y purinoceptor 1 / ADORA2B mediated anti-inflammatory cytokines production / G beta:gamma signalling through PI3Kgamma / adenylate cyclase-activating dopamine receptor signaling pathway / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / 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 / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / retina development in camera-type eye / G protein activity / presynaptic membrane / GTPase binding / Ca2+ pathway / fibroblast proliferation / scaffold protein binding / midbody / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / cell cortex / G alpha (i) signalling events / G alpha (s) signalling events / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (q) signalling events / chemical synaptic transmission / 加水分解酵素; 酸無水物に作用; GTPに作用・細胞または細胞小器官の運動に関与 / 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 類似検索 - 分子機能 | ||||||||||||||||||
| 生物種 |  Homo sapiens (ヒト) /   Lama glama (ラマ) | ||||||||||||||||||
| 手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.5 Å | ||||||||||||||||||
|  データ登録者 | Lin S / Han S | ||||||||||||||||||
| 資金援助 |  中国, 5件 
 | ||||||||||||||||||
|  引用 |  ジャーナル: Nature / 年: 2021 タイトル: Structures of G-bound metabotropic glutamate receptors mGlu2 and mGlu4. 著者: Shuling Lin / Shuo Han / Xiaoqing Cai / Qiuxiang Tan / Kexiu Zhou / Dejian Wang / Xinwei Wang / Juan Du / Cuiying Yi / Xiaojing Chu / Antao Dai / Yan Zhou / Yan Chen / Yu Zhou / Hong Liu / ...著者: Shuling Lin / Shuo Han / Xiaoqing Cai / Qiuxiang Tan / Kexiu Zhou / Dejian Wang / Xinwei Wang / Juan Du / Cuiying Yi / Xiaojing Chu / Antao Dai / Yan Zhou / Yan Chen / Yu Zhou / Hong Liu / Jianfeng Liu / Dehua Yang / Ming-Wei Wang / Qiang Zhao / Beili Wu /  要旨: The metabotropic glutamate receptors (mGlus) have key roles in modulating cell excitability and synaptic transmission in response to glutamate (the main excitatory neurotransmitter in the central ...The metabotropic glutamate receptors (mGlus) have key roles in modulating cell excitability and synaptic transmission in response to glutamate (the main excitatory neurotransmitter in the central nervous system). It has previously been suggested that only one receptor subunit within an mGlu homodimer is responsible for coupling to G protein during receptor activation. However, the molecular mechanism that underlies the asymmetric signalling of mGlus remains unknown. Here we report two cryo-electron microscopy structures of human mGlu2 and mGlu4 bound to heterotrimeric G protein. The structures reveal a G-protein-binding site formed by three intracellular loops and helices III and IV that is distinct from the corresponding binding site in all of the other G-protein-coupled receptor (GPCR) structures. Furthermore, we observed an asymmetric dimer interface of the transmembrane domain of the receptor in the two mGlu-G structures. We confirmed that the asymmetric dimerization is crucial for receptor activation, which was supported by functional data; this dimerization may provide a molecular basis for the asymmetric signal transduction of mGlus. These findings offer insights into receptor signalling of class C GPCRs. | ||||||||||||||||||
| 履歴 | 
 | 
- 構造の表示
構造の表示
| ムービー | 
 
 
  ムービービューア | 
|---|---|
| 構造ビューア | EMマップ:  SurfView  Molmil  Jmol/JSmol | 
| 添付画像 | 
- ダウンロードとリンク
ダウンロードとリンク
-EMDBアーカイブ
| マップデータ |  emd_31031.map.gz | 167.5 MB |  EMDBマップデータ形式 | |
|---|---|---|---|---|
| ヘッダ (付随情報) |  emd-31031-v30.xml  emd-31031.xml | 18.1 KB 18.1 KB | 表示 表示 |  EMDBヘッダ | 
| 画像 |  emd_31031.png | 40.3 KB | ||
| Filedesc metadata |  emd-31031.cif.gz | 6.8 KB | ||
| アーカイブディレクトリ |  http://ftp.pdbj.org/pub/emdb/structures/EMD-31031  ftp://ftp.pdbj.org/pub/emdb/structures/EMD-31031 | HTTPS FTP | 
-検証レポート
| 文書・要旨 |  emd_31031_validation.pdf.gz | 453 KB | 表示 |  EMDB検証レポート | 
|---|---|---|---|---|
| 文書・詳細版 |  emd_31031_full_validation.pdf.gz | 452.6 KB | 表示 | |
| XML形式データ |  emd_31031_validation.xml.gz | 4.2 KB | 表示 | |
| CIF形式データ |  emd_31031_validation.cif.gz | 4.7 KB | 表示 | |
| アーカイブディレクトリ |  https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-31031  ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-31031 | HTTPS FTP | 
-関連構造データ
- リンク
リンク
| EMDBのページ |  EMDB (EBI/PDBe) /  EMDataResource | 
|---|---|
| 「今月の分子」の関連する項目 | 
- マップ
マップ
| ファイル |  ダウンロード / ファイル: emd_31031.map.gz / 形式: CCP4 / 大きさ: 220.5 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 投影像・断面図 | 画像のコントロール
 
 画像は Spider により作成 これらの図は立方格子座標系で作成されたものです | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| ボクセルのサイズ | X=Y=Z: 1.045 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 密度 | 
 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 詳細 | EMDB XML: 
 CCP4マップ ヘッダ情報: 
 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
-添付データ
- 試料の構成要素
試料の構成要素
-全体 : Complex of mGlu2 homodimer with heterotrimeric Gi1 protein in pre...
| 全体 | 名称: Complex of mGlu2 homodimer with heterotrimeric Gi1 protein in presence of antibodies | 
|---|---|
| 要素 | 
 | 
-超分子 #1: Complex of mGlu2 homodimer with heterotrimeric Gi1 protein in pre...
| 超分子 | 名称: Complex of mGlu2 homodimer with heterotrimeric Gi1 protein in presence of antibodies タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#6 | 
|---|---|
| 由来(天然) | 生物種:  Homo sapiens (ヒト) | 
-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 | 
|---|---|
| 由来(天然) | 生物種:  Homo sapiens (ヒト) | 
| 分子量 | 理論値: 90.240281 KDa | 
| 組換発現 | 生物種:  Baculovirus expression vector pFastBac1-HM (ウイルス) | 
| 配列 | 文字列: DYKDDDDGAP EGPAKKVLTL EGDLVLGGLF PVHQKGGPAE DCGPVNEHRG IQRLEAMLFA LDRINRDPHL LPGVRLGAHI  LDSCSKDTH ALEQALDFVR ASLSRGADGS RHICPDGSYA THGDAPTAIT GVIGGSYSDV SIQVANLLRL FQIPQISYAS T SAKLSDKS  ...文字列: DYKDDDDGAP EGPAKKVLTL EGDLVLGGLF PVHQKGGPAE DCGPVNEHRG IQRLEAMLFA LDRINRDPHL LPGVRLGAHI  LDSCSKDTH ALEQALDFVR ASLSRGADGS RHICPDGSYA THGDAPTAIT GVIGGSYSDV SIQVANLLRL FQIPQISYAS T SAKLSDKS RYDYFARTVP PDFFQAKAMA EILRFFNWTY VSTVASEGDY GETGIEAFEL EARARNICVA TSEKVGRAMS RA AFEGVVR ALLQKPSARV AVLFTRSEDA RELLAASQRL NASFTWVASD GWGALESVVA GSEGAAEGAI TIELASYPIS DFA SYFQSL DPWNNSRNPW FREFWEQRFR CSFRQRDCAA HSLRAVPFEQ ESKIMFVVNA VYAMAHALHN MHRALCPNTT RLCD AMRPV NGRRLYKDFV LNVKFDAPFR PADTHNEVRF DRFGDGIGRY NIFTYLRAGS GRYRYQKVGY WAEGLTLDTS LIPWA SPSA GPLPASRCSE PCLQNEVKSV QPGEVCCWLC IPCQPYEYRL DEFTCADCGL GYWPNASLTG CFELPQEYIR WGDAWA VGP VTIACLGALA TLFVLGVFVR HNATPVVKAA GRELCYILLG GVFLCYCMTF IFIAKPSTAV CTLRRLGLGT AFSVCYS AL LTKTNRIARI FGGAREGAQR PRFISPASQV AICLALISGQ LLIVVAWLVV EAPGTGKETA PERREVVTLR CNHRDASM L GSLAYNVLLI ALCTLYAFKT RKCPENFNEA KFIGFTMYTT CIIWLAFLPI FYVTSSDYRV QTTTMCVSVS LSGSVVLGC  LFAPKLHIIL FQPQKNV UniProtKB: Metabotropic glutamate receptor 2 | 
-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 | 
|---|---|
| 由来(天然) | 生物種:  Homo sapiens (ヒト) | 
| 分子量 | 理論値: 40.414047 KDa | 
| 組換発現 | 生物種:  Baculovirus expression vector pFastBac1-HM (ウイルス) | 
| 配列 | 文字列: MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKNTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS  IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI  ...文字列: MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKNTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS  IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI PTQQDVLRTR VKTTGIVETH FTFKDLHFKM FDVGAQRSER KKWIHCFEGV TAIIFCVALS DYDLVLAEDE EM NRMHASM KLFDSICNNK WFTDTSIILF LNKKDLFEEK IKKSPLTICY PEYAGSNTYE EAAAYIQCQF EDLNKRKDTK EIY THFTCS TDTKNVQFVF DAVTDVIIKN NLKDCGLF UniProtKB: Guanine nucleotide-binding protein G(i) subunit alpha-1 | 
-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 | 
|---|---|
| 由来(天然) | 生物種:  Homo sapiens (ヒト) | 
| 分子量 | 理論値: 38.744371 KDa | 
| 組換発現 | 生物種:  Baculovirus expression vector pFastBac1-HM (ウイルス) | 
| 配列 | 文字列: MHHHHHHGSL LQSELDQLRQ EAEQLKNQIR DARKACADAT LSQITNNIDP VGRIQMRTRR TLRGHLAKIY AMHWGTDSRL  LVSASQDGK LIIWDSYTTN KVHAIPLRSS WVMTCAYAPS GNYVACGGLD NICSIYNLKT REGNVRVSRE LAGHTGYLSC C RFLDDNQI  ...文字列: MHHHHHHGSL LQSELDQLRQ EAEQLKNQIR DARKACADAT LSQITNNIDP VGRIQMRTRR TLRGHLAKIY AMHWGTDSRL  LVSASQDGK LIIWDSYTTN KVHAIPLRSS WVMTCAYAPS GNYVACGGLD NICSIYNLKT REGNVRVSRE LAGHTGYLSC C RFLDDNQI VTSSGDTTCA LWDIETGQQT TTFTGHTGDV MSLSLAPDTR LFVSGACDAS AKLWDVREGM CRQTFTGHES DI NAICFFP NGNAFATGSD DATCRLFDLR ADQELMTYSH DNIICGITSV SFSKSGRLLL AGYDDFNCNV WDALKADRAG VLA GHDNRV SCLGVTDDGM AVATGSWDSF LKIWN UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 | 
-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 | 
|---|---|
| 由来(天然) | 生物種:  Homo sapiens (ヒト) | 
| 分子量 | 理論値: 7.861143 KDa | 
| 組換発現 | 生物種:  Baculovirus expression vector pFastBac1-HM (ウイルス) | 
| 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 #5: scFv16
| 分子 | 名称: scFv16 / タイプ: protein_or_peptide / ID: 5 / コピー数: 1 / 光学異性体: LEVO | 
|---|---|
| 由来(天然) | 生物種:  Homo sapiens (ヒト) | 
| 分子量 | 理論値: 27.409588 KDa | 
| 組換発現 | 生物種:  Baculovirus expression vector pFastBac1-HM (ウイルス) | 
| 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 KAAALEVLFQ | 
-分子 #6: DN13
| 分子 | 名称: DN13 / タイプ: protein_or_peptide / ID: 6 / コピー数: 2 / 光学異性体: LEVO | 
|---|---|
| 由来(天然) | 生物種:   Lama glama (ラマ) | 
| 分子量 | 理論値: 13.637166 KDa | 
| 組換発現 | 生物種:   Escherichia coli (大腸菌) | 
| 配列 | 文字列: QVQLVQSGGG LVQAGGSLRL SCAASVRFFS INTMGWYRQA PGKQRELVAD ITSSGSTNYA DSGKGRFTIS RDNAKNTVYL  QMNRLKPED TAVYYCHADY KYTTHNTAWG QGTQVTVSSL EVLFQ | 
-分子 #7: (1S,2S,5R,6S)-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid
| 分子 | 名称: (1S,2S,5R,6S)-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid タイプ: ligand / ID: 7 / コピー数: 2 / 式: 40F | 
|---|---|
| 分子量 | 理論値: 185.177 Da | 
| Chemical component information |  ChemComp-40F:  | 
-分子 #8: 1-butyl-3-chloranyl-4-(4-phenylpiperidin-1-yl)pyridin-2-one
| 分子 | 名称: 1-butyl-3-chloranyl-4-(4-phenylpiperidin-1-yl)pyridin-2-one タイプ: ligand / ID: 8 / コピー数: 1 / 式: HZR | 
|---|---|
| 分子量 | 理論値: 344.878 Da | 
| Chemical component information |  ChemComp-HZR:  | 
-実験情報
-構造解析
| 手法 | クライオ電子顕微鏡法 | 
|---|---|
|  解析 | 単粒子再構成法 | 
| 試料の集合状態 | particle | 
- 試料調製
試料調製
| 緩衝液 | pH: 7.4 | 
|---|---|
| 凍結 | 凍結剤: ETHANE | 
- 電子顕微鏡法
電子顕微鏡法
| 顕微鏡 | FEI TITAN KRIOS | 
|---|---|
| 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: 70.0 e/Å2 | 
| 電子線 | 加速電圧: 300 kV / 電子線源:  FIELD EMISSION GUN | 
| 電子光学系 | 照射モード: SPOT SCAN / 撮影モード: BRIGHT FIELD | 
| 実験機器 |  モデル: Titan Krios / 画像提供: FEI Company | 
- 画像解析
画像解析
| 初期モデル | モデルのタイプ: INSILICO MODEL | 
|---|---|
| 最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 3.5 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 850700 | 
| 初期 角度割当 | タイプ: MAXIMUM LIKELIHOOD | 
| 最終 角度割当 | タイプ: ANGULAR RECONSTITUTION | 
 ムービー
ムービー コントローラー
コントローラー









































 Z (Sec.)
Z (Sec.) Y (Row.)
Y (Row.) X (Col.)
X (Col.)





















