+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-32838 | |||||||||
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タイトル | Tethered peptide activation mechanism of adhesion GPCRs ADGRG2 and ADGRG4 | |||||||||
マップデータ | Cryo-EM structure of the ADGRG2-beta-Gs complex | |||||||||
試料 |
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機能・相同性 | 機能・相同性情報 PKA activation in glucagon signalling / hair follicle placode formation / developmental growth / D1 dopamine receptor binding / intracellular transport / renal water homeostasis / Hedgehog 'off' state / adenylate cyclase-activating adrenergic receptor signaling pathway / activation of adenylate cyclase activity / cellular response to glucagon stimulus ...PKA activation in glucagon signalling / hair follicle placode formation / developmental growth / D1 dopamine receptor binding / intracellular transport / renal water homeostasis / Hedgehog 'off' state / adenylate cyclase-activating adrenergic receptor signaling pathway / activation of adenylate cyclase activity / cellular response to glucagon stimulus / adenylate cyclase activator activity / regulation of insulin secretion / trans-Golgi network membrane / G protein-coupled receptor activity / negative regulation of inflammatory response to antigenic stimulus / bone development / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / adenylate cyclase-activating 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-coupled acetylcholine receptor signaling pathway / G protein activity / G-protein activation / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / platelet aggregation / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / cognition / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Sensory perception of sweet, bitter, and umami (glutamate) taste / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / photoreceptor disc membrane / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / cellular response to catecholamine stimulus / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / 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 / cellular response to prostaglandin E stimulus / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / sensory perception of smell / G alpha (12/13) signalling events / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / positive regulation of cold-induced thermogenesis / retina development in camera-type eye / Ca2+ pathway / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / 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 / G alpha (q) signalling events / Ras protein signal transduction / cell population proliferation / Extra-nuclear estrogen signaling / cell surface receptor signaling pathway / G protein-coupled receptor signaling pathway / apical plasma membrane / lysosomal membrane / GTPase activity / synapse / protein-containing complex binding / GTP binding / signal transduction / extracellular exosome / membrane / metal ion binding / plasma membrane / cytosol / cytoplasm 類似検索 - 分子機能 | |||||||||
生物種 | Homo sapiens (ヒト) / Lama glama (ラマ) / Mus musculus (ハツカネズミ) | |||||||||
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 | |||||||||
データ登録者 | He QT / Guo SC / Xiao P / Sun JP / Yu X / Gou L / Kong LL / Zhang L | |||||||||
資金援助 | 中国, 2件
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引用 | ジャーナル: Nature / 年: 2022 タイトル: Tethered peptide activation mechanism of the adhesion GPCRs ADGRG2 and ADGRG4. 著者: Peng Xiao / Shengchao Guo / Xin Wen / Qing-Tao He / Hui Lin / Shen-Ming Huang / Lu Gou / Chao Zhang / Zhao Yang / Ya-Ni Zhong / Chuan-Cheng Yang / Yu Li / Zheng Gong / Xiao-Na Tao / Zhi-Shuai ...著者: Peng Xiao / Shengchao Guo / Xin Wen / Qing-Tao He / Hui Lin / Shen-Ming Huang / Lu Gou / Chao Zhang / Zhao Yang / Ya-Ni Zhong / Chuan-Cheng Yang / Yu Li / Zheng Gong / Xiao-Na Tao / Zhi-Shuai Yang / Yan Lu / Shao-Long Li / Jun-Yan He / Chuanxin Wang / Lei Zhang / Liangliang Kong / Jin-Peng Sun / Xiao Yu / 要旨: Adhesion G protein-coupled receptors (aGPCRs) constitute an evolutionarily ancient family of receptors that often undergo autoproteolysis to produce α and β subunits. A tethered agonism mediated by ...Adhesion G protein-coupled receptors (aGPCRs) constitute an evolutionarily ancient family of receptors that often undergo autoproteolysis to produce α and β subunits. A tethered agonism mediated by the 'Stachel sequence' of the β subunit has been proposed to have central roles in aGPCR activation. Here we present three cryo-electron microscopy structures of aGPCRs coupled to the G heterotrimer. Two of these aGPCRs are activated by tethered Stachel sequences-the ADGRG2-β-G complex and the ADGRG4-β-G complex (in which β indicates the β subunit of the aGPCR)-and the other is the full-length ADGRG2 in complex with the exogenous ADGRG2 Stachel-sequence-derived peptide agonist IP15 (ADGRG2(FL)-IP15-G). The Stachel sequences of both ADGRG2-β and ADGRG4-β assume a U shape and insert deeply into the seven-transmembrane bundles. Constituting the FXφφφXφ motif (in which φ represents a hydrophobic residue), five residues of ADGRG2-β or ADGRG4-β extend like fingers to mediate binding to the seven-transmembrane domain and activation of the receptor. The structure of the ADGRG2(FL)-IP15-G complex reveals the structural basis for the improved binding affinity of IP15 compared with VPM-p15 and indicates that rational design of peptidic agonists could be achieved by exploiting aGPCR-β structures. By converting the 'finger residues' to acidic residues, we develop a method to generate peptidic antagonists towards several aGPCRs. Collectively, our study provides structural and biochemical insights into the tethered activation mechanism of aGPCRs. | |||||||||
履歴 |
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-構造の表示
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 | emd_32838.map.gz | 25.3 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-32838-v30.xml emd-32838.xml | 18.8 KB 18.8 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_32838.png | 17.9 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-32838 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-32838 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_32838_validation.pdf.gz | 464 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_32838_full_validation.pdf.gz | 463.6 KB | 表示 | |
XML形式データ | emd_32838_validation.xml.gz | 4.9 KB | 表示 | |
CIF形式データ | emd_32838_validation.cif.gz | 5.7 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-32838 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-32838 | HTTPS FTP |
-関連構造データ
-リンク
EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
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「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_32838.map.gz / 形式: CCP4 / 大きさ: 27 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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注釈 | Cryo-EM structure of the ADGRG2-beta-Gs 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 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
-試料の構成要素
-全体 : ADGRG2-beta-Gs complex
全体 | 名称: ADGRG2-beta-Gs complex |
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要素 |
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-超分子 #1: ADGRG2-beta-Gs complex
超分子 | 名称: ADGRG2-beta-Gs complex / タイプ: complex / キメラ: Yes / ID: 1 / 親要素: 0 / 含まれる分子: all |
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分子量 | 実験値: 134 KDa |
-超分子 #2: Gs
超分子 | 名称: Gs / タイプ: complex / キメラ: Yes / ID: 2 / 親要素: 1 / 含まれる分子: #1-#3 |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
組換発現 | 生物種: Baculovirus expression vector pFastBac1-HM (ウイルス) |
-超分子 #3: Nanobody-35
超分子 | 名称: Nanobody-35 / タイプ: complex / キメラ: Yes / ID: 3 / 親要素: 1 / 含まれる分子: #4 |
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由来(天然) | 生物種: Lama glama (ラマ) |
組換発現 | 生物種: Escherichia phage EcSzw-2 (ファージ) |
-超分子 #4: Adhesion G-protein coupled receptor G2
超分子 | 名称: Adhesion G-protein coupled receptor G2 / タイプ: complex / キメラ: Yes / ID: 4 / 親要素: 1 / 含まれる分子: #5 |
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由来(天然) | 生物種: Mus musculus (ハツカネズミ) |
組換発現 | 生物種: Baculovirus expression vector pFastBac1-HM (ウイルス) |
-分子 #1: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
分子 | 名称: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short 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: Homo sapiens (ヒト) |
分子量 | 理論値: 45.683434 KDa |
組換発現 | 生物種: Baculovirus expression vector pFastBac1-HM (ウイルス) |
配列 | 文字列: MGCLGNSKTE DQRNEEKAQR EANKKIEKQL QKDKQVYRAT HRLLLLGAGE SGKNTIVKQM RILHVNGFNG EGGEEDPQAA RSNSDGEKA TKVQDIKNNL KEAIETIVAA MSNLVPPVEL ANPENQFRVD YILSVMNVPD FDFPPEFYEH AKALWEDEGV R ACYERSNE ...文字列: MGCLGNSKTE DQRNEEKAQR EANKKIEKQL QKDKQVYRAT HRLLLLGAGE SGKNTIVKQM RILHVNGFNG EGGEEDPQAA RSNSDGEKA TKVQDIKNNL KEAIETIVAA MSNLVPPVEL ANPENQFRVD YILSVMNVPD FDFPPEFYEH AKALWEDEGV R ACYERSNE YQLIDCAQYF LDKIDVIKQA DYVPSDQDLL RCRVLTSGIF ETKFQVDKVN FHMFDVGAQR DERRKWIQCF ND VTAIIFV VASSSYNMVI REDNQTNRLQ AALKLFDSIW NNKWLRDTSV ILFLNKQDLL AEKVLAGKSK IEDYFPEFAR YTT PEDATP EPGEDPRVTR AKYFIRDEFL RISTASGDGR HYCYPHFTCA VDTENIRRVF NDCRDIIQRM HLRQYELL |
-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: Homo sapiens (ヒト) |
分子量 | 理論値: 39.48916 KDa |
組換発現 | 生物種: Baculovirus expression vector pFastBac1-HM (ウイルス) |
配列 | 文字列: MHHHHHHLEV LFQGPGSSQS ELDQLRQEAE QLKNQIRDAR KACADATLSQ ITNNIDPVGR IQMRTRRTLR GHLAKIYAMH WGTDSRLLV SASQDGKLII WDSYTTNKVH AIPLRSSWVM TCAYAPSGNY VACGGLDNIC SIYNLKTREG NVRVSRELAG H TGYLSCCR ...文字列: MHHHHHHLEV LFQGPGSSQS ELDQLRQEAE QLKNQIRDAR KACADATLSQ ITNNIDPVGR IQMRTRRTLR GHLAKIYAMH WGTDSRLLV SASQDGKLII WDSYTTNKVH AIPLRSSWVM TCAYAPSGNY VACGGLDNIC SIYNLKTREG NVRVSRELAG H TGYLSCCR FLDDNQIVTS SGDTTCALWD IETGQQTTTF TGHTGDVMSL SLAPDTRLFV SGACDASAKL WDVREGMCRQ TF TGHESDI NAICFFPNGN AFATGSDDAT CRLFDLRADQ ELMTYSHDNI ICGITSVSFS KSGRLLLAGY DDFNCNVWDA LKA DRAGVL AGHDNRVSCL GVTDDGMAVA TGSWDSFLKI WN |
-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: 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 |
-分子 #4: Nanobody-35
分子 | 名称: Nanobody-35 / 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: Lama glama (ラマ) |
分子量 | 理論値: 13.885439 KDa |
組換発現 | 生物種: Escherichia phage EcSzw-2 (ファージ) |
配列 | 文字列: QVQLQESGGG LVQPGGSLRL SCAASGFTFS NYKMNWVRQA PGKGLEWVSD ISQSGASISY TGSVKGRFTI SRDNAKNTLY LQMNSLKPE DTAVYYCARC PAPFTRDCFD VTSTTYAYRG QGTQVTVSS |
-分子 #5: Adhesion G-protein coupled receptor G2,mCherry
分子 | 名称: Adhesion G-protein coupled receptor G2,mCherry / タイプ: protein_or_peptide / ID: 5 詳細: residues 1010-1017 = His tag, residues 1018-1020 = linker, residues 1021-1027 = TEV site コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: Mus musculus (ハツカネズミ) |
分子量 | 理論値: 77.147891 KDa |
組換発現 | 生物種: Baculovirus expression vector pFastBac1-HM (ウイルス) |
配列 | 文字列: MKTIIALSYI FCLVFAHLTS FGILLDLSRT SLPPSQMMAL TFITYIGCGL SSIFLSVTLV TYIAFEKIRR DYPSKILIQL CAALLLLNL IFLLDSWIAL YNTRGFCIAV AVFLHYFLLV SFTWMGLEAF HMYLALVKVF NTYIRKYILK FCIVGWGIPA V VVSIVLTI ...文字列: MKTIIALSYI FCLVFAHLTS FGILLDLSRT SLPPSQMMAL TFITYIGCGL SSIFLSVTLV TYIAFEKIRR DYPSKILIQL CAALLLLNL IFLLDSWIAL YNTRGFCIAV AVFLHYFLLV SFTWMGLEAF HMYLALVKVF NTYIRKYILK FCIVGWGIPA V VVSIVLTI SPDNYGIGSY GKFPNGTPDD FCWINSNVVF YITVVGYFCV IFLLNVSMFI VVLVQLCRIK KKKQLGAQRK TS IQDLRSI AGLTFLLGIT WGFAFFAWGP VNVTFMYLFA IFNTLQGFFI FIFYCAAKEN VRKQWRRYLC CGKLRLAENS DWS KTATNG LKKQTVNQGV SSSSNSLQSS CNSTNSTTLL VNSDCSVHAS GNGNASTERN GVSFSVQNGD VCLHDLTGKQ HMFS DKEDS CNGKSRIALR RTSKRGSLHF IEQMHHHHHH HHGSAENLYF QGMVSKGEED NMAIIKEFMR FKVHMEGSVN GHEFE IEGE GEGRPYEGTQ TAKLKVTKGG PLPFAWDILS PQFMYGSKAY VKHPADIPDY LKLSFPEGFK WERVMNFEDG GVVTVT QDS SLQDGEFIYK VKLRGTNFPS DGPVMQKKTM GWEASSERMY PEDGALKGEI KQRLKLKDGG HYDAEVKTTY KAKKPVQ LP GAYNVNIKLD ITSHNEDYTI VEQYERAEGR HSTGGMDELY K |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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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 |
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凍結 | 凍結剤: ETHANE |
-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 K2 SUMMIT (4k x 4k) 平均電子線量: 64.0 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): 2.5 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 |
-画像解析
初期モデル | モデルのタイプ: PDB ENTRY PDBモデル - PDB ID: |
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最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 2.9 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 3743997 |
初期 角度割当 | タイプ: ANGULAR RECONSTITUTION |
最終 角度割当 | タイプ: ANGULAR RECONSTITUTION |