+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-36177 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
タイトル | Cryo-EM structure of Gi1-bound metabotropic glutamate receptor mGlu4 | |||||||||
マップデータ | ||||||||||
試料 |
| |||||||||
キーワード | Complex structure / Gi-bound metabotropic glutamate receptor mGlu4 / MEMBRANE PROTEIN | |||||||||
機能・相同性 | 機能・相同性情報 adenylate cyclase-inhibiting G protein-coupled glutamate receptor signaling pathway / adenylate cyclase inhibiting G protein-coupled glutamate receptor activity / negative regulation of adenylate cyclase activity / G protein-coupled glutamate receptor signaling pathway / neurotransmitter secretion / Class C/3 (Metabotropic glutamate/pheromone receptors) / glutamate receptor activity / GTP metabolic process / G protein-coupled dopamine receptor signaling pathway / positive regulation of macroautophagy ...adenylate cyclase-inhibiting G protein-coupled glutamate receptor signaling pathway / adenylate cyclase inhibiting G protein-coupled glutamate receptor activity / negative regulation of adenylate cyclase activity / G protein-coupled glutamate receptor signaling pathway / neurotransmitter secretion / Class C/3 (Metabotropic glutamate/pheromone receptors) / glutamate receptor activity / GTP metabolic process / G protein-coupled dopamine receptor signaling pathway / positive regulation of macroautophagy / Adenylate cyclase inhibitory pathway / regulation of neuron apoptotic process / regulation of synaptic transmission, glutamatergic / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / G protein-coupled receptor binding / G protein-coupled receptor activity / 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 / 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) / presynapse / GTPase binding / retina development in camera-type eye / phospholipase C-activating G protein-coupled receptor signaling pathway / Ca2+ pathway / midbody / G alpha (i) signalling events / fibroblast proliferation / cytoplasmic vesicle / G alpha (s) signalling events / G alpha (q) signalling events / chemical synaptic transmission / cell population proliferation / Ras protein signal transduction / positive regulation of MAPK cascade / Extra-nuclear estrogen signaling / cell cycle / G protein-coupled receptor signaling pathway / cell division / lysosomal membrane / GTPase activity / centrosome / synapse / protein-containing complex binding / nucleolus / GTP binding / Golgi apparatus / signal transduction / extracellular exosome / nucleoplasm / membrane / metal ion binding / plasma membrane / cytoplasm / cytosol 類似検索 - 分子機能 | |||||||||
生物種 | Homo sapiens (ヒト) / Escherichia coli (大腸菌) | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.4 Å | |||||||||
データ登録者 | Wang X / Wang M / Xu T / Feng Y / Han S / Lin S / Zhao Q / Wu B | |||||||||
資金援助 | 中国, 2件
| |||||||||
引用 | ジャーナル: Cell Res / 年: 2023 タイトル: Structural insights into dimerization and activation of the mGlu2-mGlu3 and mGlu2-mGlu4 heterodimers. 著者: Xinwei Wang / Mu Wang / Tuo Xu / Ye Feng / Qiang Shao / Shuo Han / Xiaojing Chu / Yechun Xu / Shuling Lin / Qiang Zhao / Beili Wu / 要旨: Heterodimerization of the metabotropic glutamate receptors (mGlus) has shown importance in the functional modulation of the receptors and offers potential drug targets for treating central nervous ...Heterodimerization of the metabotropic glutamate receptors (mGlus) has shown importance in the functional modulation of the receptors and offers potential drug targets for treating central nervous system diseases. However, due to a lack of molecular details of the mGlu heterodimers, understanding of the mechanisms underlying mGlu heterodimerization and activation is limited. Here we report twelve cryo-electron microscopy (cryo-EM) structures of the mGlu2-mGlu3 and mGlu2-mGlu4 heterodimers in different conformational states, including inactive, intermediate inactive, intermediate active and fully active conformations. These structures provide a full picture of conformational rearrangement of mGlu2-mGlu3 upon activation. The Venus flytrap domains undergo a sequential conformational change, while the transmembrane domains exhibit a substantial rearrangement from an inactive, symmetric dimer with diverse dimerization patterns to an active, asymmetric dimer in a conserved dimerization mode. Combined with functional data, these structures reveal that stability of the inactive conformations of the subunits and the subunit-G protein interaction pattern are determinants of asymmetric signal transduction of the heterodimers. Furthermore, a novel binding site for two mGlu4 positive allosteric modulators was observed in the asymmetric dimer interfaces of the mGlu2-mGlu4 heterodimer and mGlu4 homodimer, and may serve as a drug recognition site. These findings greatly extend our knowledge about signal transduction of the mGlus. | |||||||||
履歴 |
|
-構造の表示
添付画像 |
---|
-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_36177.map.gz | 160.3 MB | EMDBマップデータ形式 | |
---|---|---|---|---|
ヘッダ (付随情報) | emd-36177-v30.xml emd-36177.xml | 17.2 KB 17.2 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_36177.png | 46.2 KB | ||
Filedesc metadata | emd-36177.cif.gz | 6.8 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-36177 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-36177 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_36177_validation.pdf.gz | 467.2 KB | 表示 | EMDB検証レポート |
---|---|---|---|---|
文書・詳細版 | emd_36177_full_validation.pdf.gz | 466.8 KB | 表示 | |
XML形式データ | emd_36177_validation.xml.gz | 7.1 KB | 表示 | |
CIF形式データ | emd_36177_validation.cif.gz | 8.1 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-36177 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-36177 | HTTPS FTP |
-関連構造データ
関連構造データ | 8jd6MC 8jcuC 8jcvC 8jcwC 8jcxC 8jcyC 8jczC 8jd0C 8jd1C 8jd2C 8jd3C 8jd4C 8jd5C C: 同じ文献を引用 (文献) M: このマップから作成された原子モデル |
---|---|
類似構造データ | 類似検索 - 機能・相同性F&H 検索 |
-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
ファイル | ダウンロード / ファイル: emd_36177.map.gz / 形式: CCP4 / 大きさ: 178 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
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:
|
-添付データ
-試料の構成要素
-全体 : Gi1-bound metabotropic glutamate receptor mGlu4
全体 | 名称: Gi1-bound metabotropic glutamate receptor mGlu4 |
---|---|
要素 |
|
-超分子 #1: Gi1-bound metabotropic glutamate receptor mGlu4
超分子 | 名称: Gi1-bound metabotropic glutamate receptor mGlu4 / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#5 |
---|---|
由来(天然) | 生物種: Homo sapiens (ヒト) |
-分子 #1: Metabotropic glutamate receptor 4
分子 | 名称: Metabotropic glutamate receptor 4 / 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: 99.458359 KDa |
組換発現 | 生物種: Baculovirus expression vector pFastBac1-HM (ウイルス) |
配列 | 文字列: DYKDDDDGAP KPKGHPHMNS IRIDGDITLG GLFPVHGRGS EGKPCGELKK EKGIHRLEAM LFALDRINND PDLLPNITLG ARILDTCSR DTHALEQSLT FVQALIEKDG TEVRCGSGGP PIITKPERVV GVIGASGSSV SIMVANILRL FKIPQISYAS T APDLSDNS ...文字列: DYKDDDDGAP KPKGHPHMNS IRIDGDITLG GLFPVHGRGS EGKPCGELKK EKGIHRLEAM LFALDRINND PDLLPNITLG ARILDTCSR DTHALEQSLT FVQALIEKDG TEVRCGSGGP PIITKPERVV GVIGASGSSV SIMVANILRL FKIPQISYAS T APDLSDNS RYDFFSRVVP SDTYQAQAMV DIVRALKWNY VSTVASEGSY GESGVEAFIQ KSREDGGVCI AQSVKIPREP KA GEFDKII RRLLETSNAR AVIIFANEDD IRRVLEAARR ANQTGHFFWM GSDSWGSKIA PVLHLEEVAE GAVTILPKRM SVR GFDRYF SSRTLDNNRR NIWFAEFWED NFHCKLSRHA LKKGSHVKKC TNRERIGQDS AYEQEGKVQF VIDAVYAMGH ALHA MHRDL CPGRVGLCPR MDPVDGTQLL KYIRNVNFSG IAGNPVTFNE NGDAPGRYDI YQYQLRNDSA EYKVIGSWTD HLHLR IERM HWPGSGQQLP RSICSLPCQP GERKKTVKGM PCCWHCEPCT GYQYQVDRYT CKTCPYDMRP TENRTGCRPI PIIKLE WGS PWAVLPLFLA VVGIAATLFV VITFVRYNDT PIVKASGREL SYVLLAGIFL CYATTFLMIA EPDLGTCSLR RIFLGLG MS ISYAALLTKT NRIYRIFEQG KRSVSAPRFI SPASQLAITF SLISLQLLGI CVWFVVDPSH SVVDFQDQRT LDPRFARG V LKCDISDLSL ICLLGYSMLL MVTCTVYAIK TRGVPETFNE AKPIGFTMYT TCIVWLAFIP IFFGTSQSAD KLYIQTTTL TVSVSLSASV SLGMLYMPKV YIILFHPEQN VPKRKRSLKA VVTAATMSNK FTQKGNFRPN GEAKSELCEN LEAPALATKQ TYVTYTNHA I UniProtKB: Metabotropic glutamate receptor 4 |
-分子 #2: scFv
分子 | 名称: scFv / 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: Escherichia coli (大腸菌) |
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 #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 |
---|---|
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 #4: 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: 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: 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 #5: 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: 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: 40.55207 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 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 FTDKDLYFKM 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 #6: N-(3-chlorophenyl)pyridine-2-carboxamide
分子 | 名称: N-(3-chlorophenyl)pyridine-2-carboxamide / タイプ: ligand / ID: 6 / コピー数: 1 / 式: BK0 |
---|---|
分子量 | 理論値: 232.666 Da |
Chemical component information | ChemComp-BK0: |
-分子 #7: PHOSPHOSERINE
分子 | 名称: PHOSPHOSERINE / タイプ: ligand / ID: 7 / コピー数: 2 / 式: SEP |
---|---|
分子量 | 理論値: 185.072 Da |
Chemical component information | ChemComp-SEP: |
-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
緩衝液 | pH: 7.5 |
---|---|
凍結 | 凍結剤: ETHANE |
-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 / 最大 デフォーカス(公称値): 1.5 µm / 最小 デフォーカス(公称値): 0.8 µm |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
-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: 3.4 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 839200 |
初期 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |