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データを開く
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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 | |||||||||
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![]() | SIGNALING PROTEIN / G protein-coupled receptor / Chemokine receptor CCR5 / RANTES | |||||||||
機能・相同性 | ![]() 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 / 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 / negative regulation by host of viral transcription / 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 / response to cholesterol / positive regulation of innate immune response / cellular response to fibroblast growth factor stimulus / positive regulation of monocyte chemotaxis / chemokine-mediated signaling pathway / Chemokine receptors bind chemokines / release of sequestered calcium ion into cytosol by sarcoplasmic reticulum / chemokine activity / 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 / exocytosis / monocyte chemotaxis / Interleukin-10 signaling / regulation of insulin secretion / positive regulation of phosphorylation / positive regulation of cell adhesion / cellular response to interleukin-1 / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / positive regulation of T cell migration / Binding and entry of HIV virion / positive regulation of translational initiation / regulation of cAMP-mediated signaling / cellular defense response / positive regulation of viral genome replication / D2 dopamine receptor binding / G protein-coupled serotonin receptor binding / coreceptor activity / positive regulation of T cell proliferation / positive regulation of epithelial cell proliferation / positive regulation of tyrosine phosphorylation of STAT protein / regulation of mitotic spindle organization / cellular response to forskolin / epithelial cell proliferation / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / positive regulation of smooth muscle cell proliferation / cell chemotaxis / Regulation of insulin secretion / G protein-coupled receptor binding / calcium-mediated signaling / positive regulation of receptor signaling pathway via JAK-STAT / response to virus / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G protein-coupled acetylcholine receptor signaling pathway / G-protein activation / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / response to toxic substance / cellular response to virus / cellular response to type II interferon / response to peptide hormone / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) 類似検索 - 分子機能 | |||||||||
生物種 | ![]() | |||||||||
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 | |||||||||
![]() | Zhang, H. / Chen, K. / Tan, Q. / Han, S. / Zhu, Y. / Zhao, Q. / Wu, B. | |||||||||
資金援助 | ![]()
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![]() | ![]() 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
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構造ビューア | 分子: ![]() ![]() |
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ダウンロードとリンク
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PDBx/mmCIF形式 | ![]() | 182.7 KB | 表示 | ![]() |
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PDB形式 | ![]() | 140.1 KB | 表示 | ![]() |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
その他 | ![]() |
-検証レポート
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
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-関連構造データ
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リンク
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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) ![]() 発現宿主: ![]() ![]() 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) ![]() 発現宿主: ![]() ![]() 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) ![]() 発現宿主: ![]() ![]() 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) ![]() 発現宿主: ![]() ![]() 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 |
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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: ![]() |
由来(組換発現) | 生物種: ![]() ![]() |
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 |
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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: ![]() |
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) |
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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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