+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 7f1r | |||||||||
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タイトル | Cryo-EM structure of the chemokine receptor CCR5 in complex with RANTES and Gi | |||||||||
要素 |
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キーワード | SIGNALING PROTEIN / G protein-coupled receptor / Chemokine receptor CCR5 / RANTES | |||||||||
機能・相同性 | 機能・相同性情報 regulation of chronic inflammatory response / CCR4 chemokine receptor binding / chemokine receptor antagonist activity / activation of phospholipase D activity / chemokine (C-C motif) ligand 5 binding / positive regulation of cellular biosynthetic process / CCR1 chemokine receptor binding / positive regulation of natural killer cell chemotaxis / negative regulation of macrophage apoptotic process / chemokine receptor binding ...regulation of chronic inflammatory response / CCR4 chemokine receptor binding / chemokine receptor antagonist activity / activation of phospholipase D activity / chemokine (C-C motif) ligand 5 binding / positive regulation of cellular biosynthetic process / CCR1 chemokine receptor binding / positive regulation of natural killer cell chemotaxis / negative regulation of macrophage apoptotic process / chemokine receptor binding / signaling / cell surface receptor signaling pathway via STAT / chemokine receptor activity / positive regulation of cell-cell adhesion mediated by integrin / receptor signaling protein tyrosine kinase activator activity / CCR5 chemokine receptor binding / positive regulation of T cell chemotaxis / positive regulation of homotypic cell-cell adhesion / CCR chemokine receptor binding / C-C chemokine receptor activity / neutrophil activation / C-C chemokine binding / positive regulation of G protein-coupled receptor signaling pathway / phosphatidylinositol phospholipase C activity / negative regulation of T cell apoptotic process / positive regulation of T cell apoptotic process / positive regulation of calcium ion transport / eosinophil chemotaxis / positive regulation of innate immune response / response to cholesterol / cellular response to fibroblast growth factor stimulus / chemokine-mediated signaling pathway / positive regulation of monocyte chemotaxis / Chemokine receptors bind chemokines / chemokine activity / release of sequestered calcium ion into cytosol by sarcoplasmic reticulum / regulation of T cell activation / dendritic cell chemotaxis / negative regulation of G protein-coupled receptor signaling pathway / leukocyte cell-cell adhesion / negative regulation of viral genome replication / phospholipase activator activity / positive regulation of macrophage chemotaxis / macrophage chemotaxis / positive regulation of smooth muscle cell migration / chemoattractant activity / monocyte chemotaxis / exocytosis / Interleukin-10 signaling / regulation of insulin secretion / cellular response to interleukin-1 / negative regulation by host of viral transcription / positive regulation of T cell migration / Binding and entry of HIV virion / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / positive regulation of translational initiation / cellular defense response / regulation of cAMP-mediated signaling / positive regulation of viral genome replication / coreceptor activity / D2 dopamine receptor binding / G protein-coupled serotonin receptor binding / positive regulation of T cell proliferation / positive regulation of tyrosine phosphorylation of STAT protein / positive regulation of phosphorylation / regulation of mitotic spindle organization / cellular response to forskolin / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / positive regulation of cell adhesion / G-protein beta/gamma-subunit complex binding / cell chemotaxis / positive regulation of epithelial cell proliferation / epithelial cell proliferation / Regulation of insulin secretion / G protein-coupled receptor binding / positive regulation of smooth muscle cell proliferation / calcium-mediated signaling / response to virus / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / Olfactory Signaling Pathway / Activation of the phototransduction cascade / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / Glucagon signaling in metabolic regulation / G protein-coupled acetylcholine receptor signaling pathway / G-protein activation / cellular response to virus / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / cellular response to type II interferon / G beta:gamma signalling through CDC42 / response to peptide hormone / Vasopressin regulates renal water homeostasis via Aquaporins / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Glucagon-type ligand receptors 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 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
ムービー |
ムービービューア |
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構造ビューア | 分子: MolmilJmol/JSmol |
-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 7f1r.cif.gz | 182.7 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7f1r.ent.gz | 140.1 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7f1r.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 | 7f1r_validation.pdf.gz | 788.1 KB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 7f1r_full_validation.pdf.gz | 795.1 KB | 表示 | |
XML形式データ | 7f1r_validation.xml.gz | 29.4 KB | 表示 | |
CIF形式データ | 7f1r_validation.cif.gz | 43.3 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/f1/7f1r ftp://data.pdbj.org/pub/pdb/validation_reports/f1/7f1r | HTTPS FTP |
-関連構造データ
-リンク
-集合体
登録構造単位 |
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-要素
#1: タンパク質 | 分子量: 52101.227 Da / 分子数: 1 / 変異: F28C,G258N,E267C / 由来タイプ: 組換発現 / 詳細: Fusion protein of RANTES and CCR5 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: CCL5, D17S136E, SCYA5, CCR5, CMKBR5 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: P13501, UniProt: P51681 |
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#2: タンパク質 | 分子量: 40447.141 Da / 分子数: 1 / 変異: S47C,G202T,G203A,E245A,A326S / 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) 参照: UniProt: P63096 |
#3: タンパク質 | 分子量: 37416.930 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: GNB1 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: P62873 |
#4: タンパク質 | 分子量: 7861.143 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: GNG2 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: P59768 |
-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: Chemokine receptor CCR5 in complex with RANTES 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: 7.5 |
試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
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: SPOT SCAN |
電子レンズ | モード: BRIGHT FIELD |
撮影 | 電子線照射量: 2.1875 e/Å2 フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) |
-解析
CTF補正 | タイプ: NONE | ||||||||||||||||||||||||
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3次元再構成 | 解像度: 3 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 1304062 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
精密化 | 立体化学のターゲット値: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
原子変位パラメータ | Biso mean: 59.52 Å2 | ||||||||||||||||||||||||
拘束条件 |
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