+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-34663 | |||||||||
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タイトル | Cryo-EM structure of endothelin1-bound ETAR-Gq complex | |||||||||
マップデータ | ||||||||||
試料 |
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キーワード | ET1 / ETAR / Gq / scFv16 / MEMBRANE PROTEIN | |||||||||
機能・相同性 | 機能・相同性情報 regulation of protein localization to cell leading edge / : / endothelin receptor activity / positive regulation of prostaglandin-endoperoxide synthase activity / endothelin A receptor binding / protein kinase C deactivation / cellular response to human chorionic gonadotropin stimulus / meiotic cell cycle process involved in oocyte maturation / phospholipase D-activating G protein-coupled receptor signaling pathway / rhythmic excitation ...regulation of protein localization to cell leading edge / : / endothelin receptor activity / positive regulation of prostaglandin-endoperoxide synthase activity / endothelin A receptor binding / protein kinase C deactivation / cellular response to human chorionic gonadotropin stimulus / meiotic cell cycle process involved in oocyte maturation / phospholipase D-activating G protein-coupled receptor signaling pathway / rhythmic excitation / endothelin B receptor binding / peptide hormone secretion / neural crest cell fate commitment / sympathetic neuron axon guidance / positive regulation of artery morphogenesis / Oplophorus-luciferin 2-monooxygenase / Oplophorus-luciferin 2-monooxygenase activity / glomerular endothelium development / vein smooth muscle contraction / body fluid secretion / noradrenergic neuron differentiation / response to prostaglandin F / semaphorin-plexin signaling pathway involved in axon guidance / positive regulation of sarcomere organization / vascular associated smooth muscle cell development / atrial cardiac muscle tissue development / positive regulation of renal sodium excretion / leukocyte activation / histamine secretion / heparin metabolic process / positive regulation of chemokine-mediated signaling pathway / maternal process involved in parturition / cardiac chamber formation / rough endoplasmic reticulum lumen / pharyngeal arch artery morphogenesis / regulation of glucose transmembrane transport / positive regulation of odontogenesis / endothelin receptor signaling pathway involved in heart process / epithelial fluid transport / cardiac neural crest cell migration involved in outflow tract morphogenesis / negative regulation of hormone secretion / endothelin receptor signaling pathway / Weibel-Palade body / response to leptin / developmental pigmentation / podocyte differentiation / sodium ion homeostasis / response to acetylcholine / response to ozone / renal sodium ion absorption / glomerular filtration / positive regulation of cell growth involved in cardiac muscle cell development / artery smooth muscle contraction / podocyte apoptotic process / mesenchymal cell apoptotic process / left ventricular cardiac muscle tissue morphogenesis / embryonic skeletal system development / protein transmembrane transport / enteric nervous system development / axonogenesis involved in innervation / positive regulation of cation channel activity / cellular response to follicle-stimulating hormone stimulus / cellular response to luteinizing hormone stimulus / cranial skeletal system development / positive regulation of prostaglandin secretion / renal albumin absorption / negative regulation of nitric-oxide synthase biosynthetic process / cellular response to mineralocorticoid stimulus / basal part of cell / respiratory gaseous exchange by respiratory system / positive regulation of smooth muscle contraction / response to salt / positive regulation of urine volume / sympathetic nervous system development / regulation of pH / phosphatidylinositol phospholipase C activity / norepinephrine metabolic process / positive regulation of hormone secretion / regulation of systemic arterial blood pressure by endothelin / vasoconstriction / : / embryonic heart tube development / negative regulation of blood coagulation / axon extension / dorsal/ventral pattern formation / establishment of endothelial barrier / superoxide anion generation / positive regulation of neutrophil chemotaxis / positive regulation of signaling receptor activity / : / cartilage development / middle ear morphogenesis / cellular response to glucocorticoid stimulus / aorta development / negative regulation of protein metabolic process / prostaglandin biosynthetic process / cellular response to fatty acid / neuromuscular process / nitric oxide transport / branching involved in blood vessel morphogenesis 類似検索 - 分子機能 | |||||||||
生物種 | Homo (哺乳類) / Homo sapiens (ヒト) / 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: 3.01 Å | |||||||||
データ登録者 | Yuan Q / Jiang Y / Xu HE / Ji Y / Duan J | |||||||||
資金援助 | 中国, 1件
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引用 | ジャーナル: Nat Commun / 年: 2023 タイトル: Structural basis of peptide recognition and activation of endothelin receptors. 著者: Yujie Ji / Jia Duan / Qingning Yuan / Xinheng He / Gong Yang / Shengnan Zhu / Kai Wu / Wen Hu / Tianyu Gao / Xi Cheng / Hualiang Jiang / H Eric Xu / Yi Jiang / 要旨: Endothelin system comprises three endogenous 21-amino-acid peptide ligands endothelin-1, -2, and -3 (ET-1/2/3), and two G protein-coupled receptor (GPCR) subtypes-endothelin receptor A (ETR) and B ...Endothelin system comprises three endogenous 21-amino-acid peptide ligands endothelin-1, -2, and -3 (ET-1/2/3), and two G protein-coupled receptor (GPCR) subtypes-endothelin receptor A (ETR) and B (ETR). Since ET-1, the first endothelin, was identified in 1988 as one of the most potent endothelial cell-derived vasoconstrictor peptides with long-lasting actions, the endothelin system has attracted extensive attention due to its critical role in vasoregulation and close relevance in cardiovascular-related diseases. Here we present three cryo-electron microscopy structures of ETR and ETR bound to ET-1 and ETR bound to the selective peptide IRL1620. These structures reveal a highly conserved recognition mode of ET-1 and characterize the ligand selectivity by ETRs. They also present several conformation features of the active ETRs, thus revealing a specific activation mechanism. Together, these findings deepen our understanding of endothelin system regulation and offer an opportunity to design selective drugs targeting specific ETR subtypes. | |||||||||
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_34663.map.gz | 56.6 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-34663-v30.xml emd-34663.xml | 20 KB 20 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_34663.png | 37.6 KB | ||
Filedesc metadata | emd-34663.cif.gz | 6.6 KB | ||
その他 | emd_34663_half_map_1.map.gz emd_34663_half_map_2.map.gz | 49.6 MB 49.4 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-34663 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-34663 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_34663_validation.pdf.gz | 800.6 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_34663_full_validation.pdf.gz | 800.2 KB | 表示 | |
XML形式データ | emd_34663_validation.xml.gz | 12.3 KB | 表示 | |
CIF形式データ | emd_34663_validation.cif.gz | 14.4 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-34663 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-34663 | 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_34663.map.gz / 形式: CCP4 / 大きさ: 64 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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ボクセルのサイズ | X=Y=Z: 0.824 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
-ハーフマップ: #2
ファイル | emd_34663_half_map_1.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: #1
ファイル | emd_34663_half_map_2.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-試料の構成要素
-全体 : ET1-ETAR-Gq-scFv16 complex
全体 | 名称: ET1-ETAR-Gq-scFv16 complex |
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要素 |
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-超分子 #1: ET1-ETAR-Gq-scFv16 complex
超分子 | 名称: ET1-ETAR-Gq-scFv16 complex / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #6, #5, #1-#4 |
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由来(天然) | 生物種: Homo (哺乳類) |
-分子 #1: Guanine nucleotide-binding protein G(q) subunit alpha-1
分子 | 名称: Guanine nucleotide-binding protein G(q) subunit alpha-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: Homo sapiens (ヒト) |
分子量 | 理論値: 28.084832 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
配列 | 文字列: MGSTVSAEDK AAAERSKMID KNLREDGEKA RRTLRLLLLG ADNSGKSTIV KQMRILHGGS GGSGGTSGIF ETKFQVDKVN FHMFDVGGQ RDERRKWIQC FNDVTAIIFV VDSSDYNRLQ EALNDFKSIW NNRWLRTISV ILFLNKQDLL AEKVLAGKSK I EDYFPEFA ...文字列: MGSTVSAEDK AAAERSKMID KNLREDGEKA RRTLRLLLLG ADNSGKSTIV KQMRILHGGS GGSGGTSGIF ETKFQVDKVN FHMFDVGGQ RDERRKWIQC FNDVTAIIFV VDSSDYNRLQ EALNDFKSIW NNRWLRTISV ILFLNKQDLL AEKVLAGKSK I EDYFPEFA RYTTPEDATP EPGEDPRVTR AKYFIRKEFV DISTASGDGR HICYPHFTCA VDTENARRIF NDCKDIILQM NL REYNLV |
-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: 41.055867 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
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 LKIWNGSSGG GGSGGGGSSG VSGWRLFKKI S UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 |
-分子 #3: scFv16
分子 | 名称: scFv16 / 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: Mus musculus (ハツカネズミ) |
分子量 | 理論値: 30.363043 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
配列 | 文字列: MLLVNQSHQG FNKEHTSKMV SAIVLYVLLA AAAHSAFAVQ LVESGGGLVQ PGGSRKLSCS ASGFAFSSFG MHWVRQAPEK GLEWVAYIS SGSGTIYYAD TVKGRFTISR DDPKNTLFLQ MTSLRSEDTA MYYCVRSIYY YGSSPFDFWG QGTTLTVSAG G GGSGGGGS ...文字列: MLLVNQSHQG FNKEHTSKMV SAIVLYVLLA AAAHSAFAVQ LVESGGGLVQ PGGSRKLSCS ASGFAFSSFG MHWVRQAPEK GLEWVAYIS SGSGTIYYAD TVKGRFTISR DDPKNTLFLQ MTSLRSEDTA MYYCVRSIYY YGSSPFDFWG QGTTLTVSAG G GGSGGGGS GGGGSADIVM TQATSSVPVT PGESVSISCR SSKSLLHSNG NTYLYWFLQR PGQSPQLLIY RMSNLASGVP DR FSGSGSG TAFTLTISRL EAEDVGVYYC MQHLEYPLTF GAGTKLEL |
-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: Homo sapiens (ヒト) |
分子量 | 理論値: 7.861143 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
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: Endothelin-1
分子 | 名称: Endothelin-1 / 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: Homo sapiens (ヒト) |
分子量 | 理論値: 2.497951 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
配列 | 文字列: CSCSSLMDKE CVYFCHLDII W UniProtKB: Endothelin-1 |
-分子 #6: Endothelin-1 receptor,Oplophorus-luciferin 2-monooxygenase cataly...
分子 | 名称: Endothelin-1 receptor,Oplophorus-luciferin 2-monooxygenase catalytic subunit chimera タイプ: protein_or_peptide / ID: 6 / コピー数: 1 / 光学異性体: LEVO / EC番号: Oplophorus-luciferin 2-monooxygenase |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 69.969906 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
配列 | 文字列: MDSKGSSQKG SRLLLLLVVS NLLLCQGVVS DYKDDDDVDM GQPGNGSAFL LAPNGSHAPD HDVTQQRDEE NLYFQGASDN PERYSTNLS NHVDDFTTFR GTELSFLVTT HQPTNLVLPS NGSMHNYCPQ QTKITSAFKY INTVISCTIF IVGMVGNATL L RIIYQNKC ...文字列: MDSKGSSQKG SRLLLLLVVS NLLLCQGVVS DYKDDDDVDM GQPGNGSAFL LAPNGSHAPD HDVTQQRDEE NLYFQGASDN PERYSTNLS NHVDDFTTFR GTELSFLVTT HQPTNLVLPS NGSMHNYCPQ QTKITSAFKY INTVISCTIF IVGMVGNATL L RIIYQNKC MRNGPNALIA SLALGDLIYV VIDLPINVFK LLAGRWPFDH NDFGVFLCKL FPFLQKSSVG ITVLNLCALS VD RYRAVAS WSRVQGIGIP LVTAIEIVSI WILSFILAIP EAIGFVMVPF EYRGEQHKTC MLNATSKFME FYQDVKDWWL FGF YFCMPL VCTAIFYTLM TCEMLNRRNG SLRIALSEHL KQRREVAKTV FCLVVIFALC WFPLHLSRIL KKTVYNEMDK NRCE LLSFL LLMDYIGINL ATMNSCINPI ALYFVSKKFK NCFQSCLCCC CYQSKSLMTS VPMNGTSIQV FTLEDFVGDW EQTAA YNLD QVLEQGGVSS LLQNLAVSVT PIQRIVRSGE NALKIDIHVI IPYEGLSADQ MAQIEEVFKV VYPVDDHHFK VILPYG TLV IDGVTPNMLN YFGRPYEGIA VFDGKKITVT GTLWNGNKII DERLITPDGS MLFRVTINS UniProtKB: Endothelin-1 receptor, Oplophorus-luciferin 2-monooxygenase catalytic subunit |
-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: 7.4 |
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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 K3 BIOQUANTUM (6k x 4k) 平均電子線量: 50.0 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: FLOOD BEAM / 撮影モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 1.8 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: OTHER |
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最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 3.01 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 510197 |
初期 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |