+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 8iy6 | ||||||
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タイトル | ETB-Gi complex bound to Endotheline-1, focused on receptor | ||||||
要素 |
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キーワード | PEPTIDE BINDING PROTEIN / Class A GPCR / Endothelin / 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 / phospholipase D-activating G protein-coupled receptor signaling pathway / rhythmic excitation / peptide hormone secretion / endothelin B receptor binding / cellular response to human chorionic gonadotropin stimulus / meiotic cell cycle process involved in oocyte maturation / positive regulation of artery morphogenesis ...positive regulation of prostaglandin-endoperoxide synthase activity / endothelin A receptor binding / protein kinase C deactivation / phospholipase D-activating G protein-coupled receptor signaling pathway / rhythmic excitation / peptide hormone secretion / endothelin B receptor binding / cellular response to human chorionic gonadotropin stimulus / meiotic cell cycle process involved in oocyte maturation / positive regulation of artery morphogenesis / semaphorin-plexin signaling pathway involved in axon guidance / body fluid secretion / neural crest cell fate commitment / vein smooth muscle contraction / glomerular endothelium development / response to prostaglandin F / sympathetic neuron axon guidance / positive regulation of sarcomere organization / noradrenergic neuron differentiation / positive regulation of renal sodium excretion / histamine secretion / leukocyte activation / maternal process involved in parturition / positive regulation of chemokine-mediated signaling pathway / rough endoplasmic reticulum lumen / pharyngeal arch artery morphogenesis / regulation of D-glucose transmembrane transport / positive regulation of odontogenesis / epithelial fluid transport / endothelin receptor signaling pathway involved in heart process / negative regulation of hormone secretion / cardiac neural crest cell migration involved in outflow tract morphogenesis / Weibel-Palade body / response to leptin / endothelin receptor signaling pathway / response to ozone / podocyte differentiation / positive regulation of cell growth involved in cardiac muscle cell development / renal sodium ion absorption / artery smooth muscle contraction / glomerular filtration / axonogenesis involved in innervation / positive regulation of cation channel activity / cellular response to follicle-stimulating hormone stimulus / cellular response to luteinizing hormone stimulus / negative regulation of nitric-oxide synthase biosynthetic process / regulation of pH / positive regulation of prostaglandin secretion / respiratory gaseous exchange by respiratory system / basal part of cell / cellular response to mineralocorticoid stimulus / positive regulation of smooth muscle contraction / response to salt / positive regulation of urine volume / positive regulation of hormone secretion / regulation of systemic arterial blood pressure by endothelin / vasoconstriction / negative regulation of blood coagulation / : / embryonic heart tube development / dorsal/ventral pattern formation / axon extension / superoxide anion generation / positive regulation of neutrophil chemotaxis / positive regulation of signaling receptor activity / cartilage development / middle ear morphogenesis / cellular response to glucocorticoid stimulus / negative regulation of protein metabolic process / prostaglandin biosynthetic process / cellular response to fatty acid / nitric oxide transport / positive regulation of heart rate / branching involved in blood vessel morphogenesis / positive regulation of cardiac muscle hypertrophy / response to dexamethasone / response to testosterone / negative regulation of smooth muscle cell apoptotic process / thyroid gland development / membrane depolarization / positive regulation of cell size / cellular response to interleukin-1 / regulation of vasoconstriction / response to amino acid / canonical Wnt signaling pathway / Transcriptional and post-translational regulation of MITF-M expression and activity / positive regulation of JUN kinase activity / cellular response to transforming growth factor beta stimulus / positive regulation of vascular associated smooth muscle cell proliferation / transport vesicle / protein kinase A signaling / response to muscle stretch / response to amphetamine / ERK1 and ERK2 cascade / positive regulation of calcium-mediated signaling / phosphatidylinositol 3-kinase/protein kinase B signal transduction / positive regulation of endothelial cell migration / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / positive regulation of mitotic nuclear division / cellular response to calcium ion 類似検索 - 分子機能 | ||||||
生物種 | Homo sapiens (ヒト) | ||||||
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: 3.13 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 | 8iy6.cif.gz | 93.8 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb8iy6.ent.gz | 61.1 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 8iy6.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
文書・要旨 | 8iy6_validation.pdf.gz | 1022.8 KB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 8iy6_full_validation.pdf.gz | 1 MB | 表示 | |
XML形式データ | 8iy6_validation.xml.gz | 19.4 KB | 表示 | |
CIF形式データ | 8iy6_validation.cif.gz | 27.6 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/iy/8iy6 ftp://data.pdbj.org/pub/pdb/validation_reports/iy/8iy6 | HTTPS FTP |
-関連構造データ
関連構造データ | 35815MC 8iy5C 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
#1: 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) 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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#2: 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, and Gi / タイプ: COMPLEX / Entity ID: all / 由来: RECOMBINANT |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
由来(組換発現) | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
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 FIELD / 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 |
試料ホルダ | 凍結剤: NITROGEN |
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: 3.13 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: 3.13→3.13 Å / Cor.coef. Fo:Fc: 0.877 / SU B: 20.883 / SU ML: 0.372 / ESU R: 0.39 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: 84.927 Å2 | ||||||||||||||||||||||||
精密化ステップ | サイクル: 1 / 合計: 2495 | ||||||||||||||||||||||||
拘束条件 |
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LS精密化 シェル | 解像度: 3→3.078 Å / Total num. of bins used: 20 /
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