+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 9c3e | |||||||||||||||||||||
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タイトル | TCR - CD3 complex bound to HLA | |||||||||||||||||||||
要素 |
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キーワード | IMMUNE SYSTEM / T-cell receptor / TCR / 1G4 / nanodisc / CD3 / HLA / NY-ESO-1 | |||||||||||||||||||||
機能・相同性 | 機能・相同性情報 tRNA threonylcarbamoyladenosine metabolic process / 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 / CD4-positive, alpha-beta T cell proliferation / gamma-delta T cell activation / Fc-gamma receptor signaling pathway ...tRNA threonylcarbamoyladenosine metabolic process / 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 / CD4-positive, alpha-beta T cell proliferation / gamma-delta T cell activation / Fc-gamma receptor signaling pathway / 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 / establishment or maintenance of cell polarity / smoothened signaling pathway / positive regulation of interleukin-4 production / Translocation of ZAP-70 to Immunological synapse / Phosphorylation of CD3 and TCR zeta chains / dendrite development / 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 T cell proliferation / negative regulation of smoothened signaling pathway / cell surface receptor protein tyrosine kinase signaling pathway / T cell costimulation / positive regulation of interleukin-2 production / positive regulation of calcium-mediated signaling / T cell activation / FCGR3A-mediated IL10 synthesis / cerebellum development / protein tyrosine kinase binding / positive regulation of ferrous iron binding / positive regulation of transferrin receptor binding / negative regulation of receptor binding / DAP12 interactions / antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-independent / positive regulation of receptor binding / antigen processing and presentation of endogenous peptide antigen via MHC class Ib / early endosome lumen / Nef mediated downregulation of MHC class I complex cell surface expression / cellular response to iron ion / Endosomal/Vacuolar pathway / Antigen Presentation: Folding, assembly and peptide loading of class I MHC / apoptotic signaling pathway / FCGR3A-mediated phagocytosis / calcium-mediated signaling / clathrin-coated endocytic vesicle membrane / cellular response to iron(III) ion / protein complex oligomerization / antigen processing and presentation of exogenous protein antigen via MHC class Ib, TAP-dependent / negative regulation of forebrain neuron differentiation / regulation of erythrocyte differentiation / peptide antigen assembly with MHC class I protein complex / ER to Golgi transport vesicle membrane / 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 / positive regulation of T cell cytokine production / antigen processing and presentation of endogenous peptide antigen via MHC class I / sensory perception of smell / Regulation of actin dynamics for phagocytic cup formation / MHC class I protein complex / negative regulation of neurogenesis / multicellular organismal-level iron ion homeostasis / positive regulation of receptor-mediated endocytosis / peptide antigen assembly with MHC class II protein complex / SH3 domain binding / MHC class II protein complex / cellular response to nicotine / positive regulation of T cell mediated cytotoxicity / positive regulation of type II interferon production / specific granule lumen / phagocytic vesicle membrane / recycling endosome membrane / peptide antigen binding / positive regulation of peptidyl-tyrosine phosphorylation / positive regulation of cellular senescence / antigen processing and presentation of exogenous peptide antigen via MHC class II / negative regulation of epithelial cell proliferation / transmembrane signaling receptor activity / Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell / Interferon gamma signaling / positive regulation of immune response / positive regulation of T cell activation / cell-cell junction / Modulation by Mtb of host immune system / protein transport 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: 3.5 Å | |||||||||||||||||||||
データ登録者 | Notti, R.Q. / Walz, T. | |||||||||||||||||||||
資金援助 | 米国, 6件
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引用 | ジャーナル: bioRxiv / 年: 2024 タイトル: The resting and ligand-bound states of the membrane-embedded human T-cell receptor-CD3 complex. 著者: Ryan Q Notti / Fei Yi / Søren Heissel / Martin W Bush / Zaki Molvi / Pujita Das / Henrik Molina / Christopher A Klebanoff / Thomas Walz 要旨: The T-cell receptor (TCR) initiates T-lymphocyte activation, but mechanistic questions remain( ). Here, we present cryogenic electron microscopy structures for the unliganded and human leukocyte ...The T-cell receptor (TCR) initiates T-lymphocyte activation, but mechanistic questions remain( ). Here, we present cryogenic electron microscopy structures for the unliganded and human leukocyte antigen (HLA)-bound human TCR-CD3 complex in nanodiscs that provide a native-like lipid environment. Distinct from the "open and extended" conformation seen in detergent( ), the unliganded TCR-CD3 in nanodiscs adopts two related "closed and compacted" conformations that represent its physiologic resting state . By contrast, the HLA-bound complex adopts the open and extended conformation, and conformation-locking disulfide mutants show that ectodomain opening is necessary for maximal ligand-dependent T-cell activation. Together, these results reveal allosteric conformational change during TCR activation and highlight the importance of native-like lipid environments for membrane protein structure determination. | |||||||||||||||||||||
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 | 9c3e.cif.gz | 288.4 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb9c3e.ent.gz | 215.5 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 9c3e.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 | 9c3e_validation.pdf.gz | 1.5 MB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 9c3e_full_validation.pdf.gz | 1.5 MB | 表示 | |
XML形式データ | 9c3e_validation.xml.gz | 60.5 KB | 表示 | |
CIF形式データ | 9c3e_validation.cif.gz | 88.9 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/c3/9c3e ftp://data.pdbj.org/pub/pdb/validation_reports/c3/9c3e | 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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1 |
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-要素
-タンパク質 , 3種, 3分子 ABH
#1: タンパク質 | 分子量: 30214.033 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 細胞株 (発現宿主): HEK293F / 発現宿主: Homo sapiens (ヒト) |
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#2: タンパク質 | 分子量: 62121.918 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 細胞株 (発現宿主): HEK293F / 発現宿主: Homo sapiens (ヒト) |
#7: タンパク質 | 分子量: 62221.281 Da / 分子数: 1 / Mutation: C9V / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) 遺伝子: CTAG1A, CTAG, CTAG1, ESO1, LAGE2, LAGE2A, CTAG1B, LAGE2B, B2M, CDABP0092, HDCMA22P, HLA-A 細胞株 (発現宿主): HEK293F / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P78358, UniProt: P61769, UniProt: H9BNV4 |
-T-cell surface glycoprotein CD3 ... , 4種, 6分子 DEFGXY
#3: タンパク質 | 分子量: 13836.026 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 / 細胞株 (発現宿主): HEK293F / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P04234 | ||||
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#4: 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 / 細胞株 (発現宿主): HEK293F / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P07766 #5: タンパク質 | | 分子量: 22041.098 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 / 細胞株 (発現宿主): HEK293F / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P09693 #6: タンパク質 | 分子量: 18723.439 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: CD247, CD3Z, T3Z, TCRZ / 細胞株 (発現宿主): HEK293F / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P20963 |
-糖 , 2種, 9分子
#8: 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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#9: 糖 | ChemComp-NAG / |
-非ポリマー , 1種, 2分子
#10: 化合物 |
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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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配列の詳細 | The authors state that the fusion protein was provided by a commercial supplier. The linker lengths ...The authors state that the fusion protein was provided by a commercial supplier. The linker lengths and sequences are unknown. |
-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: TCR - CD3 complex in nanodisc bound to NY-ESO-1, B2M, HLA-A*02:01 single chain trimer タイプ: COMPLEX / Entity ID: #1-#7 / 由来: RECOMBINANT | |||||||||||||||
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分子量 | 実験値: NO | |||||||||||||||
由来(天然) | 生物種: Homo sapiens (ヒト) | |||||||||||||||
由来(組換発現) | 生物種: Homo sapiens (ヒト) / 株: HEK293F | |||||||||||||||
緩衝液 | pH: 7.5 | |||||||||||||||
緩衝液成分 |
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試料 | 濃度: 0.7 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES | |||||||||||||||
試料支持 | グリッドの材料: COPPER / グリッドのサイズ: 400 divisions/in. / グリッドのタイプ: Quantifoil R1.2/1.3 | |||||||||||||||
急速凍結 | 装置: FEI VITROBOT MARK IV / 凍結剤: ETHANE / 湿度: 100 % / 凍結前の試料温度: 277 K |
-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: FLOOD BEAM |
電子レンズ | モード: BRIGHT FIELD / 倍率(公称値): 64000 X / 最大 デフォーカス(公称値): 2500 nm / 最小 デフォーカス(公称値): 800 nm / Cs: 0 mm |
撮影 | 電子線照射量: 51 e/Å2 / フィルム・検出器のモデル: GATAN K3 (6k x 4k) |
-解析
EMソフトウェア | 名称: PHENIX / バージョン: 1.21_5207: / カテゴリ: モデル精密化 | ||||||||||||||||||||||||
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CTF補正 | タイプ: NONE | ||||||||||||||||||||||||
3次元再構成 | 解像度: 3.5 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 155000 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
拘束条件 |
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