+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-28571 | |||||||||
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タイトル | CryoEM structure of PN45545 TCR-CD3 in complex with HLA-A2 MAGEA4 (230-239) | |||||||||
マップデータ | ||||||||||
試料 |
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キーワード | TCR / membrane protein (膜タンパク質) / CD3 / HLA / MHC / IMMUNE SYSTEM (免疫系) | |||||||||
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 / antigen processing and presentation / FCGR activation / PD-1 signaling / Role of phospholipids in phagocytosis / positive regulation of cell cycle / negative regulation of smoothened signaling pathway / positive regulation of calcium-mediated signaling / 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 / positive regulation of ferrous iron binding / positive regulation of transferrin receptor binding / positive regulation of receptor binding / early endosome lumen / Nef mediated downregulation of MHC class I complex cell surface expression / DAP12 interactions / negative regulation of receptor binding / calcium-mediated signaling / lumenal side of endoplasmic reticulum membrane / apoptotic signaling pathway / Endosomal/Vacuolar pathway / Antigen Presentation: Folding, assembly and peptide loading of class I MHC / FCGR3A-mediated phagocytosis / clathrin-coated endocytic vesicle membrane / antigen processing and presentation of exogenous protein antigen via MHC class Ib, TAP-dependent / cellular response to iron(III) ion / negative regulation of forebrain neuron differentiation / ER to Golgi transport vesicle membrane / peptide antigen assembly with MHC class I protein complex / response to molecule of bacterial origin / regulation of erythrocyte differentiation / regulation of iron ion transport / MHC class I peptide loading complex / HFE-transferrin receptor complex / T cell mediated cytotoxicity / cellular response to iron ion / antigen processing and presentation of endogenous peptide antigen via MHC class I / Regulation of actin dynamics for phagocytic cup formation / positive regulation of T cell cytokine production / cell surface receptor protein tyrosine kinase signaling pathway / MHC class I protein complex / multicellular organismal-level iron ion homeostasis / histone deacetylase binding / SH3 domain binding / negative regulation of neurogenesis / positive regulation of T cell mediated cytotoxicity / peptide antigen assembly with MHC class II protein complex / positive regulation of receptor-mediated endocytosis / MHC class II protein complex / cellular response to nicotine / recycling endosome membrane / specific granule lumen / phagocytic vesicle membrane / peptide antigen binding / positive regulation of cellular senescence / antigen processing and presentation of exogenous peptide antigen via MHC class II / negative regulation of epithelial cell proliferation / positive regulation of type II interferon production / Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell / positive regulation of immune response / Interferon gamma signaling / Modulation by Mtb of host immune system / positive regulation of T cell activation / positive regulation of peptidyl-tyrosine phosphorylation / cell-cell junction / transmembrane signaling receptor activity / sensory perception of smell / signaling receptor complex adaptor activity 類似検索 - 分子機能 | |||||||||
生物種 | Homo sapiens (ヒト) | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 2.65 Å | |||||||||
データ登録者 | Saotome K / Franklin MC | |||||||||
資金援助 | 1件
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引用 | ジャーナル: Nat Commun / 年: 2023 タイトル: Structural analysis of cancer-relevant TCR-CD3 and peptide-MHC complexes by cryoEM. 著者: Kei Saotome / Drew Dudgeon / Kiersten Colotti / Michael J Moore / Jennifer Jones / Yi Zhou / Ashique Rafique / George D Yancopoulos / Andrew J Murphy / John C Lin / William C Olson / Matthew C Franklin / 要旨: The recognition of antigenic peptide-MHC (pMHC) molecules by T-cell receptors (TCR) initiates the T-cell mediated immune response. Structural characterization is key for understanding the specificity ...The recognition of antigenic peptide-MHC (pMHC) molecules by T-cell receptors (TCR) initiates the T-cell mediated immune response. Structural characterization is key for understanding the specificity of TCR-pMHC interactions and informing the development of therapeutics. Despite the rapid rise of single particle cryoelectron microscopy (cryoEM), x-ray crystallography has remained the preferred method for structure determination of TCR-pMHC complexes. Here, we report cryoEM structures of two distinct full-length α/β TCR-CD3 complexes bound to their pMHC ligand, the cancer-testis antigen HLA-A2/MAGEA4 (230-239). We also determined cryoEM structures of pMHCs containing MAGEA4 (230-239) peptide and the closely related MAGEA8 (232-241) peptide in the absence of TCR, which provided a structural explanation for the MAGEA4 preference displayed by the TCRs. These findings provide insights into the TCR recognition of a clinically relevant cancer antigen and demonstrate the utility of cryoEM for high-resolution structural analysis of TCR-pMHC interactions. | |||||||||
履歴 |
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-構造の表示
添付画像 |
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-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_28571.map.gz | 303.8 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-28571-v30.xml emd-28571.xml | 24.4 KB 24.4 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_28571.png | 95 KB | ||
Filedesc metadata | emd-28571.cif.gz | 7.2 KB | ||
その他 | emd_28571_half_map_1.map.gz emd_28571_half_map_2.map.gz | 260 MB 260.3 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-28571 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-28571 | HTTPS FTP |
-関連構造データ
-リンク
EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
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「今月の分子」の関連する項目 |
-マップ
ファイル | ダウンロード / ファイル: emd_28571.map.gz / 形式: CCP4 / 大きさ: 325 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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ボクセルのサイズ | X=Y=Z: 0.85 Å | ||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||
詳細 | EMDB XML:
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-添付データ
-ハーフマップ: #1
ファイル | emd_28571_half_map_1.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: #2
ファイル | emd_28571_half_map_2.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-試料の構成要素
+全体 : PN45545 TCR-CD3 complex bound to HLA-A2 MAGEA4 (230-239) with ant...
+超分子 #1: PN45545 TCR-CD3 complex bound to HLA-A2 MAGEA4 (230-239) with ant...
+分子 #1: T-cell surface glycoprotein CD3 zeta chain
+分子 #2: T-cell surface glycoprotein CD3 delta chain
+分子 #3: T-cell surface glycoprotein CD3 epsilon chain
+分子 #4: T-cell surface glycoprotein CD3 gamma chain
+分子 #5: PN45545 TCR alpha chain
+分子 #6: PN45545 TCR beta chain
+分子 #7: MHC class I antigen
+分子 #8: Beta-2-microglobulin
+分子 #9: Melanoma-associated antigen 4
+分子 #12: CHOLESTEROL HEMISUCCINATE
+分子 #13: 2-acetamido-2-deoxy-beta-D-glucopyranose
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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解析 | 単粒子再構成法 |
試料の集合状態 | particle |
-試料調製
緩衝液 | pH: 8 |
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凍結 | 凍結剤: ETHANE |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELDBright-field microscopy / 最大 デフォーカス(公称値): 2.4 µm 最小 デフォーカス(公称値): 1.4000000000000001 µm |
特殊光学系 | エネルギーフィルター - 名称: GIF Bioquantum / エネルギーフィルター - スリット幅: 20 eV |
撮影 | フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) 平均電子線量: 40.0 e/Å2 |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
-画像解析
初期モデル | モデルのタイプ: NONE |
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初期 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 2.65 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 228624 |