+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 8iy5 | ||||||
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タイトル | ETB-Gi complex bound to endothelin-1 | ||||||
要素 |
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キーワード | PEPTIDE BINDING PROTEIN / Class A GPCR / Endothelin (エンドセリン) / Gi / Vasoactive peptide | ||||||
機能・相同性 | 機能・相同性情報 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 / endothelin B receptor binding / rhythmic excitation / peptide hormone secretion / neural crest cell fate commitment ...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 / endothelin B receptor binding / rhythmic excitation / peptide hormone secretion / neural crest cell fate commitment / sympathetic neuron axon guidance / body fluid secretion / glomerular endothelium development / vein smooth muscle contraction / noradrenergic neuron differentiation / response to prostaglandin F / positive regulation of renal sodium excretion / leukocyte activation / positive regulation of sarcomere organization / histamine secretion / rough endoplasmic reticulum lumen / positive regulation of chemokine-mediated signaling pathway / maternal process involved in parturition / 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 / response to leptin / endothelin receptor signaling pathway / podocyte differentiation / response to ozone / バイベル・パラーデ小体 / 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 / axonogenesis involved in innervation / positive regulation of cation channel activity / cellular response to follicle-stimulating hormone stimulus / positive regulation of prostaglandin secretion / cellular response to luteinizing hormone stimulus / 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 / 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 / negative regulation of blood coagulation / superoxide anion generation / dorsal/ventral pattern formation / axon extension / positive regulation of neutrophil chemotaxis / middle ear morphogenesis / positive regulation of signaling receptor activity / cellular response to glucocorticoid stimulus / cartilage development / Activation of G protein gated Potassium channels / G-protein activation / G beta:gamma signalling through PI3Kgamma / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through PLC beta / ADP signalling through P2Y purinoceptor 1 / Thromboxane signalling through TP receptor / Presynaptic function of Kainate receptors / G beta:gamma signalling through CDC42 / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / G alpha (12/13) signalling events / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Thrombin signalling through proteinase activated receptors (PARs) / Ca2+ pathway / G alpha (z) signalling events / Extra-nuclear estrogen signaling / G alpha (s) signalling events / prostaglandin biosynthetic process / G alpha (q) signalling events / negative regulation of protein metabolic process / nitric oxide transport / cellular response to fatty acid / G alpha (i) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / : / branching involved in blood vessel morphogenesis / Vasopressin regulates renal water homeostasis via Aquaporins / positive regulation of heart rate / response to testosterone / response to dexamethasone 類似検索 - 分子機能 | ||||||
生物種 | Homo sapiens (ヒト) Rattus rattus (エジプトネズミ) Bos taurus (ウシ) Mus musculus (ハツカネズミ) | ||||||
手法 | 電子顕微鏡法 / 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 2.8 Å | ||||||
データ登録者 | Sano, F.K. / Akasaka, H. / Shihoya, W. / Nureki, O. | ||||||
資金援助 | 日本, 1件
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引用 | ジャーナル: Elife / 年: 2023 タイトル: Cryo-EM structure of the endothelin-1-ET-G complex. 著者: Fumiya K Sano / Hiroaki Akasaka / Wataru Shihoya / Osamu Nureki / 要旨: The endothelin ET receptor is a promiscuous G-protein coupled receptor that is activated by vasoactive peptide endothelins. ET signaling induces reactive astrocytes in the brain and vasorelaxation in ...The endothelin ET receptor is a promiscuous G-protein coupled receptor that is activated by vasoactive peptide endothelins. ET signaling induces reactive astrocytes in the brain and vasorelaxation in vascular smooth muscle. Consequently, ET agonists are expected to be drugs for neuroprotection and improved anti-tumor drug delivery. Here, we report the cryo-electron microscopy structure of the endothelin-1-ET-G complex at 2.8 Å resolution, with complex assembly stabilized by a newly established method. Comparisons with the inactive ET receptor structures revealed how endothelin-1 activates the ET receptor. The NPxxY motif, essential for G-protein activation, is not conserved in ET, resulting in a unique structural change upon G-protein activation. Compared with other GPCR-G-protein complexes, ET binds G in the shallowest position, further expanding the diversity of G-protein binding modes. This structural information will facilitate the elucidation of G-protein activation and the rational design of ET agonists. | ||||||
履歴 |
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-構造の表示
構造ビューア | 分子: MolmilJmol/JSmol |
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-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 8iy5.cif.gz | 244.4 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb8iy5.ent.gz | 185.2 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 8iy5.json.gz | ツリー表示 | PDBx/mmJSON形式 | |
その他 | その他のダウンロード |
-検証レポート
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/iy/8iy5 ftp://data.pdbj.org/pub/pdb/validation_reports/iy/8iy5 | HTTPS FTP |
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-関連構造データ
関連構造データ | 35814MC 8iy6C M: このデータのモデリングに利用したマップデータ C: 同じ文献を引用 (文献) |
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類似構造データ | 類似検索 - 機能・相同性F&H 検索 |
-リンク
-集合体
登録構造単位 |
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1 |
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-要素
-Guanine nucleotide-binding protein ... , 3種, 3分子 ABC
#1: タンパク質 | 分子量: 40415.031 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: GNAI1 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 株 (発現宿主): sf9 cells / 参照: UniProt: P63096 |
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#2: タンパク質 | 分子量: 40470.105 Da / 分子数: 1 / 由来タイプ: 組換発現 由来: (組換発現) Rattus rattus (エジプトネズミ) 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 株 (発現宿主): sf9 cells |
#3: タンパク質 | 分子量: 7563.750 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Bos taurus (ウシ) / 遺伝子: GNG2 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 株 (発現宿主): sf9 cells / 参照: UniProt: P63212 |
-抗体 / タンパク質 / タンパク質・ペプチド , 3種, 3分子 ERL
#4: 抗体 | 分子量: 27720.795 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Mus musculus (ハツカネズミ) 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 株 (発現宿主): sf9 cells |
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#5: タンパク質 | 分子量: 67492.219 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 細胞株 (発現宿主): sf9 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) |
#6: タンパク質・ペプチド | 分子量: 2497.951 Da / 分子数: 1 / 由来タイプ: 合成 / 由来: (合成) Homo sapiens (ヒト) / 参照: UniProt: P05305 |
-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
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EM実験 | 試料の集合状態: PARTICLE / 3次元再構成法: 単粒子再構成法 |
-試料調製
構成要素 | 名称: Complex of Endothelin-1, ETB, Gi trimer and scFv16 / タイプ: COMPLEX / Entity ID: all / 由来: MULTIPLE SOURCES |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
緩衝液 | pH: 8 |
試料 | 濃度: 8 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
試料支持 | グリッドの材料: GOLD / グリッドのサイズ: 300 divisions/in. / グリッドのタイプ: Quantifoil R1.2/1.3 |
急速凍結 | 凍結剤: ETHANE |
-電子顕微鏡撮影
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
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顕微鏡 | モデル: FEI TITAN KRIOS |
電子銃 | 電子線源: FIELD EMISSION GUN / 加速電圧: 300 kV / 照射モード: FLOOD BEAM |
電子レンズ | モード: BRIGHT FIELDBright-field microscopy / 倍率(公称値): 105000 X / 最大 デフォーカス(公称値): 1600 nm / 最小 デフォーカス(公称値): 800 nm / Cs: 2.7 mm |
撮影 | 平均露光時間: 2.3 sec. / 電子線照射量: 50 e/Å2 / フィルム・検出器のモデル: GATAN K3 (6k x 4k) / 実像数: 10408 |
-解析
CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
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3次元再構成 | 解像度: 2.8 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 260085 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
精密化 | 解像度: 2.8→148.74 Å / Cor.coef. Fo:Fc: 0.817 / SU B: 14.414 / SU ML: 0.28 / ESU R: 0.338 立体化学のターゲット値: MAXIMUM LIKELIHOOD WITH PHASES 詳細: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
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溶媒の処理 | 溶媒モデル: PARAMETERS FOR MASK CACLULATION | ||||||||||||||||||||||||
原子変位パラメータ | Biso mean: 119.348 Å2 | ||||||||||||||||||||||||
精密化ステップ | サイクル: 1 / 合計: 9077 | ||||||||||||||||||||||||
拘束条件 |
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LS精密化 シェル | 解像度: 2.8→2.873 Å / Total num. of bins used: 20 /
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