+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-34667 | |||||||||
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タイトル | Cryo-EM structure of Endothelin1-bound ETBR-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 (膜タンパク質) | |||||||||
機能・相同性 | 機能・相同性情報 enteric smooth muscle cell differentiation / response to endothelin / endothelin receptor activity / negative regulation of neuron maturation / aldosterone metabolic process / positive regulation of prostaglandin-endoperoxide synthase activity / endothelin A receptor binding / protein kinase C deactivation / cellular response to human chorionic gonadotropin stimulus / chordate pharynx development ...enteric smooth muscle cell differentiation / response to endothelin / endothelin receptor activity / negative regulation of neuron maturation / aldosterone metabolic process / positive regulation of prostaglandin-endoperoxide synthase activity / endothelin A receptor binding / protein kinase C deactivation / cellular response to human chorionic gonadotropin stimulus / chordate pharynx development / meiotic cell cycle process involved in oocyte maturation / phospholipase D-activating G protein-coupled receptor signaling pathway / endothelin B receptor binding / rhythmic excitation / peptide hormone secretion / neural crest cell fate commitment / sympathetic neuron axon guidance / 発光エビルシフェリン-2-モノオキシゲナーゼ / body fluid secretion / Oplophorus-luciferin 2-monooxygenase activity / glomerular endothelium development / vein smooth muscle contraction / regulation of fever generation / noradrenergic neuron differentiation / response to prostaglandin F / positive regulation of renal sodium excretion / leukocyte activation / positive regulation of sarcomere organization / histamine secretion / heparin metabolic process / rough endoplasmic reticulum lumen / positive regulation of chemokine-mediated signaling pathway / maternal process involved in parturition / positive regulation of penile erection / neuroblast migration / pharyngeal arch artery morphogenesis / regulation of glucose transmembrane transport / posterior midgut development / positive regulation of odontogenesis / endothelin receptor signaling pathway involved in heart process / protein transmembrane transport / epithelial fluid transport / cardiac neural crest cell migration involved in outflow tract morphogenesis / negative regulation of hormone secretion / response to leptin / endothelin receptor signaling pathway / podocyte differentiation / response to ozone / バイベル・パラーデ小体 / developmental pigmentation / renal sodium ion absorption / クレアチニンクリアランス / positive regulation of cell growth involved in cardiac muscle cell development / artery smooth muscle contraction / response to sodium phosphate / axonogenesis involved in innervation / enteric nervous system development / positive regulation of cation channel activity / renal sodium excretion / renin secretion into blood stream / cellular response to follicle-stimulating hormone stimulus / positive regulation of prostaglandin secretion / cellular response to luteinizing hormone stimulus / renal albumin absorption / melanocyte differentiation / negative regulation of nitric-oxide synthase biosynthetic process / cellular response to mineralocorticoid stimulus / positive regulation of urine volume / regulation of pH / respiratory gaseous exchange by respiratory system / basal part of cell / positive regulation of smooth muscle contraction / semaphorin-plexin signaling pathway involved in axon guidance / negative regulation of adenylate cyclase activity / peripheral nervous system development / positive regulation of hormone secretion / regulation of systemic arterial blood pressure by endothelin / 血管収縮 / protein kinase C-activating G protein-coupled receptor signaling pathway / embryonic heart tube development / regulation of epithelial cell proliferation / negative regulation of blood coagulation / superoxide anion generation / type 1 angiotensin receptor binding / dorsal/ventral pattern formation / establishment of endothelial barrier / axon extension / positive regulation of neutrophil chemotaxis / middle ear morphogenesis / positive regulation of signaling receptor activity / cellular response to glucocorticoid stimulus / cartilage development / 神経堤 / prostaglandin biosynthetic process / negative regulation of protein metabolic process / nitric oxide transport / cellular response to fatty acid / : / branching involved in blood vessel morphogenesis / response to pain 類似検索 - 分子機能 | |||||||||
生物種 | Homo (ヒト属) / 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: 3.5 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_34667.map.gz | 57.1 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-34667-v30.xml emd-34667.xml | 19.9 KB 19.9 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_34667.png | 42.3 KB | ||
Filedesc metadata | emd-34667.cif.gz | 6.6 KB | ||
その他 | emd_34667_half_map_1.map.gz emd_34667_half_map_2.map.gz | 49.4 MB 49.4 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-34667 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-34667 | 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_34667.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: 1.04 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_34667_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_34667_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: all |
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由来(天然) | 生物種: Homo (ヒト属) |
-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: Endothelin receptor type B,Oplophorus-luciferin 2-monooxygenase c...
分子 | 名称: Endothelin receptor type B,Oplophorus-luciferin 2-monooxygenase catalytic subunit chimera タイプ: protein_or_peptide / ID: 3 / コピー数: 1 / 光学異性体: LEVO EC番号: 発光エビルシフェリン-2-モノオキシゲナーゼ |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 67.88232 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 DYKDDDDVDH HHHHHHHEER GFPPDRATPL LQTAEIMTPP TKTLWPKGSN ASLARSLAP AEVPKGDRTA GSPPRTISPP PCQGPIEIKE TFKYINTVVS CLVFVLGIIG NSTLLRIIYK NKCMRNGPNI L IASLALGD ...文字列: MDSKGSSQKG SRLLLLLVVS NLLLCQGVVS DYKDDDDVDH HHHHHHHEER GFPPDRATPL LQTAEIMTPP TKTLWPKGSN ASLARSLAP AEVPKGDRTA GSPPRTISPP PCQGPIEIKE TFKYINTVVS CLVFVLGIIG NSTLLRIIYK NKCMRNGPNI L IASLALGD LLHIVIDIPI NVYKLLAEDW PFGAEMCKLV PFIQKASVGI TVLSLCALSI DRYRAVASWS RIKGIGVPKW TA VEIVLIW VVSVVLAVPE AIGFDIITMD YKGSYLRICL LHPVQKTAFM QFYKTAKDWW LFSFYFCLPL AITAFFYTLM TCE MLRKKS GMQIALNDHL KQRREVAKTV FCLVLVFALC WLPLHLSRIL KLTLYNQNDP NRCELLSFLL VLDYIGINMA SLNS CINPI ALYLVSKRFK NCFKSCLCCW CQSFEEKQSL EEKQSCLKFK VFTLEDFVGD WEQTAAYNLD QVLEQGGVSS LLQNL AVSV TPIQRIVRSG ENALKIDIHV IIPYEGLSAD QMAQIEEVFK VVYPVDDHHF KVILPYGTLV IDGVTPNMLN YFGRPY EGI AVFDGKKITV TGTLWNGNKI IDERLITPDG SMLFRVTINS UniProtKB: Endothelin receptor type B, Oplophorus-luciferin 2-monooxygenase catalytic subunit |
-分子 #4: Endothelin-1
分子 | 名称: Endothelin-1 / 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: 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 #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 |
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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 #6: 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: 6 / 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 |
-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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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 FIELDBright-field microscopy / 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 |
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 |
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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初期 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
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: 373655 |