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基本情報
登録情報 | データベース: PDB / ID: 8es8 | ||||||
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タイトル | CryoEM structure of PN45545 TCR-CD3 in complex with HLA-A2 MAGEA4 (230-239) | ||||||
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![]() | IMMUNE SYSTEM / TCR / membrane protein / CD3 / HLA / MHC | ||||||
機能・相同性 | ![]() 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 / alpha-beta T cell receptor complex / positive regulation of protein localization to cell surface / 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 / positive regulation of interleukin-4 production / dendrite development / Translocation of ZAP-70 to Immunological synapse / Phosphorylation of CD3 and TCR zeta chains / alpha-beta T cell activation / Generation of second messenger molecules / immunological synapse / FCGR activation / PD-1 signaling / Role of phospholipids in phagocytosis / T cell receptor binding / positive regulation of cell cycle / positive regulation of calcium-mediated signaling / negative regulation of smoothened signaling pathway / positive regulation of T cell proliferation / cell surface receptor protein tyrosine kinase signaling pathway / T cell costimulation / T cell activation / positive regulation of interleukin-2 production / cerebellum development / FCGR3A-mediated IL10 synthesis / protein tyrosine kinase binding / 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 / antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-independent / antigen processing and presentation of endogenous peptide antigen via MHC class Ib / calcium-mediated signaling / lumenal side of endoplasmic reticulum membrane / cellular response to iron ion / Endosomal/Vacuolar pathway / apoptotic signaling pathway / Antigen Presentation: Folding, assembly and peptide loading of class I MHC / FCGR3A-mediated phagocytosis / cellular response to iron(III) ion / clathrin-coated endocytic vesicle membrane / antigen processing and presentation of exogenous protein antigen via MHC class Ib, TAP-dependent / negative regulation of forebrain neuron differentiation / regulation of erythrocyte differentiation / ER to Golgi transport vesicle membrane / peptide antigen assembly with MHC class I protein complex / regulation of iron ion transport / response to molecule of bacterial origin / MHC class I peptide loading complex / HFE-transferrin receptor complex / T cell mediated cytotoxicity / antigen processing and presentation of endogenous peptide antigen via MHC class I / positive regulation of T cell cytokine production / Regulation of actin dynamics for phagocytic cup formation / MHC class I protein complex / multicellular organismal-level iron ion homeostasis / histone deacetylase binding / negative regulation of neurogenesis / peptide antigen assembly with MHC class II protein complex / positive regulation of receptor-mediated endocytosis / SH3 domain binding / MHC class II protein complex / cellular response to nicotine / positive regulation of T cell mediated cytotoxicity / specific granule lumen / recycling endosome membrane / phagocytic vesicle membrane / transmembrane signaling receptor activity / 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 peptidyl-tyrosine phosphorylation / Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell / Interferon gamma signaling / positive regulation of immune response / Modulation by Mtb of host immune system / positive regulation of type II interferon production / cell-cell junction / sensory perception of smell / protein transport 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: 2.65 Å | ||||||
![]() | Saotome, K. / Franklin, M.C. | ||||||
資金援助 | 1件
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![]() | ![]() 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. | ||||||
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構造の表示
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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ダウンロード
PDBx/mmCIF形式 | ![]() | 298.5 KB | 表示 | ![]() |
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PDB形式 | ![]() | 225.4 KB | 表示 | ![]() |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
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-検証レポート
文書・要旨 | ![]() | 1.6 MB | 表示 | ![]() |
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文書・詳細版 | ![]() | 1.6 MB | 表示 | |
XML形式データ | ![]() | 55.5 KB | 表示 | |
CIF形式データ | ![]() | 80.5 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
関連構造データ | ![]() 28571MC ![]() 8es7C ![]() 8es9C ![]() 8esaC ![]() 8esbC 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 ( |
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類似構造データ | 類似検索 - 機能・相同性 ![]() |
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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
-T-cell surface glycoprotein CD3 ... , 4種, 6分子 ZYDFEG
#1: タンパク質 | 分子量: 19654.486 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() #2: タンパク質 | | 分子量: 19150.719 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() #3: タンパク質 | 分子量: 23432.459 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() #4: タンパク質 | | 分子量: 20694.639 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() |
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-タンパク質 , 4種, 4分子 ABNM
#5: タンパク質 | 分子量: 30737.512 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() |
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#6: タンパク質 | 分子量: 35891.855 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() |
#7: タンパク質 | 分子量: 32082.512 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() |
#8: タンパク質 | 分子量: 11879.356 Da / 分子数: 1 / Fragment: UNP residues 21-119 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() |
-タンパク質・ペプチド / 非ポリマー , 2種, 2分子 P![](data/chem/img/Y01.gif)
![](data/chem/img/Y01.gif)
#12: 化合物 | ChemComp-Y01 / |
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#9: タンパク質・ペプチド | 分子量: 1134.200 Da / 分子数: 1 / Fragment: peptide (UNP residues 230-239) / 由来タイプ: 合成 / 由来: (合成) ![]() |
-糖 , 3種, 11分子 ![](data/chem/img/NAG.gif)
#10: 多糖 | beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta- ...beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose | ||
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#11: 多糖 | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose #13: 糖 | ChemComp-NAG / |
-詳細
研究の焦点であるリガンドがあるか | N |
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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 |
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試料調製
構成要素 | 名称: PN45545 TCR-CD3 complex bound to HLA-A2 MAGEA4 (230-239) with anti-Beta-2-microglobulin Fab タイプ: COMPLEX / Entity ID: #1-#9 / 由来: RECOMBINANT |
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分子量 | 実験値: NO |
由来(天然) | 生物種: ![]() |
由来(組換発現) | 生物種: ![]() |
緩衝液 | pH: 8 |
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 / 最大 デフォーカス(公称値): 2400 nm / 最小 デフォーカス(公称値): 1400 nm |
撮影 | 電子線照射量: 40 e/Å2 フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) |
電子光学装置 | 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 |
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解析
ソフトウェア |
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3次元再構成 | 解像度: 2.65 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 228624 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
精密化 | 交差検証法: NONE 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: 59.59 Å2 | ||||||||||||||||||||||||
拘束条件 |
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