+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 8wxe | ||||||
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タイトル | Vgamma5Vdelta1 EH TCR-CD3 complex | ||||||
要素 |
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キーワード | IMMUNE SYSTEM (免疫系) / immunity / receptor (受容体) | ||||||
機能・相同性 | 機能・相同性情報 regulation of lymphocyte apoptotic process / gamma-delta T cell receptor complex / Fc-gamma receptor III complex / T cell anergy / positive regulation of T cell anergy / positive regulation of cell-cell adhesion mediated by integrin / Fc-gamma receptor signaling pathway / CD4-positive, alpha-beta T cell proliferation / gamma-delta T cell activation / negative thymic T cell selection ...regulation of lymphocyte apoptotic process / gamma-delta T cell receptor complex / Fc-gamma receptor III complex / T cell anergy / positive regulation of T cell anergy / positive regulation of cell-cell adhesion mediated by integrin / Fc-gamma receptor signaling pathway / CD4-positive, alpha-beta T cell proliferation / gamma-delta T cell activation / negative thymic T cell selection / positive regulation of CD4-positive, alpha-beta T cell proliferation / positive regulation of protein localization to cell surface / alpha-beta T cell receptor complex / positive thymic T cell selection / signal complex assembly / Nef and signal transduction / positive regulation of cell-matrix adhesion / T cell receptor complex / smoothened signaling pathway / establishment or maintenance of cell polarity / Translocation of ZAP-70 to Immunological synapse / Phosphorylation of CD3 and TCR zeta chains / dendrite development / positive regulation of interleukin-4 production / Generation of second messenger molecules / alpha-beta T cell activation / 免疫シナプス / FCGR activation / PD-1 signaling / Role of phospholipids in phagocytosis / small molecule binding / negative regulation of smoothened signaling pathway / positive regulation of calcium-mediated signaling / positive regulation of phagocytosis / positive regulation of T cell proliferation / T cell receptor binding / protein tyrosine kinase binding / T cell costimulation / positive regulation of interleukin-2 production / cerebellum development / T細胞 / FCGR3A-mediated IL10 synthesis / calcium-mediated signaling / apoptotic signaling pathway / FCGR3A-mediated phagocytosis / clathrin-coated endocytic vesicle membrane / Regulation of actin dynamics for phagocytic cup formation / cell surface receptor protein tyrosine kinase signaling pathway / SH3 domain binding / peptide antigen binding / positive regulation of type II interferon production / Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell / positive regulation of T cell activation / positive regulation of peptidyl-tyrosine phosphorylation / cell-cell junction / transmembrane signaling receptor activity / signaling receptor complex adaptor activity / protein transport / Cargo recognition for clathrin-mediated endocytosis / Downstream TCR signaling / protein complex oligomerization / Clathrin-mediated endocytosis / cell body / T cell receptor signaling pathway / protein-containing complex assembly / regulation of apoptotic process / 獲得免疫系 / 樹状突起スパイン / cell surface receptor signaling pathway / 免疫応答 / G protein-coupled receptor signaling pathway / protein heterodimerization activity / external side of plasma membrane / negative regulation of gene expression / 自然免疫系 / positive regulation of gene expression / protein kinase binding / ゴルジ体 / 小胞体 / protein homodimerization activity / extracellular space / 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) | ||||||
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: 4 Å | ||||||
データ登録者 | Xin, W. / Huang, B. / Chi, X. / Xu, M. / Zhang, Y. / Li, X. / Su, Q. / Zhou, Q. | ||||||
資金援助 | 中国, 1件
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引用 | ジャーナル: Nature / 年: 2024 タイトル: Structures of human γδ T cell receptor-CD3 complex. 著者: Weizhi Xin / Bangdong Huang / Ximin Chi / Yuehua Liu / Mengjiao Xu / Yuanyuan Zhang / Xu Li / Qiang Su / Qiang Zhou / 要旨: Gamma delta (γδ) T cells, a unique T cell subgroup, are crucial in various immune responses and immunopathology. The γδ T cell receptor (TCR), which is generated by γδ T cells, recognizes a ...Gamma delta (γδ) T cells, a unique T cell subgroup, are crucial in various immune responses and immunopathology. The γδ T cell receptor (TCR), which is generated by γδ T cells, recognizes a diverse range of antigens independently of the major histocompatibility complex. The γδ TCR associates with CD3 subunits, initiating T cell activation and holding great potential in immunotherapy. Here we report the structures of two prototypical human Vγ9Vδ2 and Vγ5Vδ1 TCR-CD3 complexes, revealing two distinct assembly mechanisms that depend on Vγ usage. The Vγ9Vδ2 TCR-CD3 complex is monomeric, with considerable conformational flexibility in the TCRγ-TCRδ extracellular domain and connecting peptides. The length of the connecting peptides regulates the ligand association and T cell activation. A cholesterol-like molecule wedges into the transmembrane region, exerting an inhibitory role in TCR signalling. The Vγ5Vδ1 TCR-CD3 complex displays a dimeric architecture, whereby two protomers nestle back to back through the Vγ5 domains of the TCR extracellular domains. Our biochemical and biophysical assays further corroborate the dimeric structure. Importantly, the dimeric form of the Vγ5Vδ1 TCR is essential for T cell activation. These findings reveal organizing principles of the γδ TCR-CD3 complex, providing insights into the unique properties of γδ TCR and facilitating immunotherapeutic interventions. | ||||||
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 | 8wxe.cif.gz | 146.3 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb8wxe.ent.gz | 100 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 8wxe.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/wx/8wxe ftp://data.pdbj.org/pub/pdb/validation_reports/wx/8wxe | HTTPS FTP |
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-関連構造データ
関連構造データ | 37904MC 8jbvC 8jc0C 8jcbC 8wy0C 8wyiC 8yc0C 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
-T-cell surface glycoprotein CD3 ... , 4種, 6分子 abdefg
#1: タンパク質 | 分子量: 21809.695 Da / 分子数: 2 / 由来タイプ: 組換発現 / 詳細: 165-167: linker 168-195: twin-Strep tag / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: CD247, CD3Z, T3Z, TCRZ / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P20963 #2: タンパク質 | | 分子量: 18949.537 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: CD3D, T3D / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P04234 #3: タンパク質 | 分子量: 23174.227 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: CD3E, T3E / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P07766 #4: タンパク質 | | 分子量: 20493.457 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: CD3G, T3G / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P09693 |
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-Signal peptide,flag tag,T cell receptor ... , 2種, 2分子 mn
#5: タンパク質 | 分子量: 34320.574 Da / 分子数: 1 / 由来タイプ: 組換発現 詳細: 1-22: signal peptide, 23-31: Flag tag, 38-131: A0A1B0GX56, 155-307: B7Z8K6 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: TRDV1, TRDC / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: A0A1B0GX56, UniProt: B7Z8K6 |
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#6: タンパク質 | 分子量: 37702.062 Da / 分子数: 1 / Mutation: Y106E,R120H / 由来タイプ: 組換発現 詳細: 1-22: signal peptide, 23-31: Flag tag, 38-137: UniprotKB ID A0A0B4J1U4, 159-331: UniprotKB ID P0CF51 with Y106E and R120H 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: TRGV5, TCRGV5, TRGC1, TCRGC1 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: A0A0B4J1U4, UniProt: P0CF51 |
-非ポリマー , 1種, 1分子
#7: 化合物 | ChemComp-CLR / |
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-詳細
研究の焦点であるリガンドがあるか | Y |
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-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: T cell receptor delta 1 gamma 5 EH mutant / タイプ: COMPLEX / 詳細: Y106E and R120H in TCR gamma 5 chain / Entity ID: #1-#6 / 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: Homo sapiens (ヒト) |
緩衝液 | pH: 7.4 |
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 FIELDBright-field microscopy / 最大 デフォーカス(公称値): 2000 nm / 最小 デフォーカス(公称値): 1000 nm |
撮影 | 電子線照射量: 50 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: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3次元再構成 | 解像度: 4 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 342095 / 対称性のタイプ: POINT |