+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 7f1t | |||||||||
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タイトル | Crystal structure of the human chemokine receptor CCR5 in complex with MIP-1a | |||||||||
要素 | C-C motif chemokine 3,C-C chemokine receptor type 5,Rubredoxin,C-C chemokine receptor type 5 | |||||||||
キーワード | SIGNALING PROTEIN / G protein-coupled Receptor (Gタンパク質共役受容体) / Chemokine receptor CCR5 / MIP-1a | |||||||||
機能・相同性 | 機能・相同性情報 chemokine (C-C motif) ligand 5 binding / granulocyte chemotaxis / CCR1 chemokine receptor binding / positive regulation of microglial cell migration / positive regulation of natural killer cell chemotaxis / negative regulation of macrophage apoptotic process / regulation of behavior / signaling / astrocyte cell migration / chemokine receptor activity ...chemokine (C-C motif) ligand 5 binding / granulocyte chemotaxis / CCR1 chemokine receptor binding / positive regulation of microglial cell migration / positive regulation of natural killer cell chemotaxis / negative regulation of macrophage apoptotic process / regulation of behavior / signaling / astrocyte cell migration / chemokine receptor activity / eosinophil degranulation / CCR5 chemokine receptor binding / regulation of sensory perception of pain / negative regulation of bone mineralization / C-C chemokine receptor activity / CCR chemokine receptor binding / positive regulation of microglial cell activation / lymphocyte chemotaxis / C-C chemokine binding / cell activation / phosphatidylinositol phospholipase C activity / T cell chemotaxis / positive regulation of calcium ion transport / eosinophil chemotaxis / response to cholesterol / chemokine-mediated signaling pathway / Chemokine receptors bind chemokines / release of sequestered calcium ion into cytosol by sarcoplasmic reticulum / chemokine activity / dendritic cell chemotaxis / phospholipase activator activity / macrophage chemotaxis / positive regulation of calcium ion import / エキソサイトーシス / chemoattractant activity / negative regulation of osteoclast differentiation / Interleukin-10 signaling / monocyte chemotaxis / negative regulation by host of viral transcription / Binding and entry of HIV virion / cellular response to interleukin-1 / cellular defense response / coreceptor activity / positive regulation of calcium-mediated signaling / cytoskeleton organization / cell chemotaxis / 好中球 / positive regulation of interleukin-1 beta production / calcium-mediated signaling / response to toxic substance / intracellular calcium ion homeostasis / osteoblast differentiation / positive regulation of inflammatory response / cellular response to type II interferon / positive regulation of neuron apoptotic process / 走化性 / calcium ion transport / 分裂促進因子活性化タンパク質キナーゼ / positive regulation of tumor necrosis factor production / virus receptor activity / cell-cell signaling / cellular response to tumor necrosis factor / actin binding / kinase activity / regulation of cell shape / G alpha (i) signalling events / positive regulation of cytosolic calcium ion concentration / cellular response to lipopolysaccharide / electron transfer activity / cell surface receptor signaling pathway / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / positive regulation of ERK1 and ERK2 cascade / エンドソーム / protein kinase activity / positive regulation of cell migration / 免疫応答 / 炎症 / iron ion binding / G protein-coupled receptor signaling pathway / external side of plasma membrane / negative regulation of gene expression / positive regulation of gene expression / 細胞膜 / extracellular space / extracellular region / identical protein binding / 細胞膜 / 細胞質基質 / 細胞質 類似検索 - 分子機能 | |||||||||
生物種 | Homo sapiens (ヒト) Clostridium pasteurianum (バクテリア) | |||||||||
手法 | X線回折 / シンクロトロン / 分子置換 / 解像度: 2.6 Å | |||||||||
データ登録者 | Zhang, H. / Chen, K. / Tan, Q. / Han, S. / Zhu, Y. / Zhao, Q. / Wu, B. | |||||||||
資金援助 | 中国, 2件
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引用 | ジャーナル: Nat Commun / 年: 2021 タイトル: Structural basis for chemokine recognition and receptor activation of chemokine receptor CCR5. 著者: Hui Zhang / Kun Chen / Qiuxiang Tan / Qiang Shao / Shuo Han / Chenhui Zhang / Cuiying Yi / Xiaojing Chu / Ya Zhu / Yechun Xu / Qiang Zhao / Beili Wu / 要旨: The chemokine receptor CCR5 plays a vital role in immune surveillance and inflammation. However, molecular details that govern its endogenous chemokine recognition and receptor activation remain ...The chemokine receptor CCR5 plays a vital role in immune surveillance and inflammation. However, molecular details that govern its endogenous chemokine recognition and receptor activation remain elusive. Here we report three cryo-electron microscopy structures of G protein-coupled CCR5 in a ligand-free state and in complex with the chemokine MIP-1α or RANTES, as well as the crystal structure of MIP-1α-bound CCR5. These structures reveal distinct binding modes of the two chemokines and a specific accommodate pattern of the chemokine for the distal N terminus of CCR5. Together with functional data, the structures demonstrate that chemokine-induced rearrangement of toggle switch and plasticity of the receptor extracellular region are critical for receptor activation, while a conserved tryptophan residue in helix II acts as a trigger of receptor constitutive activation. | |||||||||
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 | 7f1t.cif.gz | 103.3 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7f1t.ent.gz | 75 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7f1t.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/f1/7f1t ftp://data.pdbj.org/pub/pdb/validation_reports/f1/7f1t | HTTPS FTP |
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-関連構造データ
-リンク
-集合体
登録構造単位 |
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1 |
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単位格子 |
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-要素
#1: タンパク質 | 分子量: 55445.453 Da / 分子数: 1 変異: T15C,T108C,C150Y,M156A,G255N,A376D,R417A,T427A,K446E 由来タイプ: 組換発現 詳細: Fusion protein of MIP-1a and CCR5 from Homo sapiens, inserted with Rubredoxin from Clostridium pasteurianum 由来: (組換発現) Homo sapiens (ヒト), (組換発現) Clostridium pasteurianum (バクテリア) 遺伝子: CCL3, G0S19-1, MIP1A, SCYA3, CCR5, CMKBR5 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: P10147, UniProt: P51681, UniProt: P00268 |
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#2: 化合物 | ChemComp-ZN / |
研究の焦点であるリガンドがあるか | N |
-実験情報
-実験
実験 | 手法: X線回折 / 使用した結晶の数: 1 |
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-試料調製
結晶 | マシュー密度: 3.01 Å3/Da / 溶媒含有率: 64.24 % |
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結晶化 | 温度: 293 K / 手法: 脂質キュービック相法 詳細: 100mM HEPES, pH 6.0, 250mM ammonium sulfate, 30% (v/v) PEG 400, 8% (v/v) PPG 400 |
-データ収集
回折 | 平均測定温度: 100 K / Serial crystal experiment: N |
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放射光源 | 由来: シンクロトロン / サイト: SPring-8 / ビームライン: BL41XU / 波長: 1 Å |
検出器 | タイプ: DECTRIS EIGER2 X 16M / 検出器: PIXEL / 日付: 2018年6月29日 |
放射 | プロトコル: SINGLE WAVELENGTH / 単色(M)・ラウエ(L): M / 散乱光タイプ: x-ray |
放射波長 | 波長: 1 Å / 相対比: 1 |
反射 | 解像度: 2.6→50 Å / Num. obs: 18209 / % possible obs: 94.9 % / 冗長度: 6.7 % / CC1/2: 0.985 / Net I/σ(I): 31.7 |
反射 シェル | 解像度: 2.6→2.64 Å / Num. unique obs: 888 / CC1/2: 0.808 |
-解析
ソフトウェア |
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精密化 | 構造決定の手法: 分子置換 開始モデル: 4MBS 解像度: 2.6→50 Å / 交差検証法: THROUGHOUT 立体化学のターゲット値: GeoStd + Monomer Library + CDL v1.2
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原子変位パラメータ | Biso mean: 117.51 Å2 | ||||||||||||||||||||||||
精密化ステップ | サイクル: LAST / 解像度: 2.6→50 Å
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拘束条件 |
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LS精密化 シェル | 解像度: 2.6→2.64 Å
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