+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 6eny | |||||||||
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タイトル | Structure of the human PLC editing module | |||||||||
要素 |
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キーワード | IMMUNE SYSTEM (免疫系) / adaptive immunity (獲得免疫系) / antigen processing / chaperone (シャペロン) / MHC class I (MHCクラスI分子) | |||||||||
機能・相同性 | 機能・相同性情報 MHC class Ib protein complex assembly / peptide antigen stabilization / Tapasin-ERp57 complex / Calnexin/calreticulin cycle / MHC class I protein complex binding / cytolytic granule / プロテインジスルフィドイソメラーゼ / Assembly of Viral Components at the Budding Site / cortical granule / positive regulation of dendritic cell chemotaxis ...MHC class Ib protein complex assembly / peptide antigen stabilization / Tapasin-ERp57 complex / Calnexin/calreticulin cycle / MHC class I protein complex binding / cytolytic granule / プロテインジスルフィドイソメラーゼ / Assembly of Viral Components at the Budding Site / cortical granule / positive regulation of dendritic cell chemotaxis / negative regulation of trophoblast cell migration / ATF6 (ATF6-alpha) activates chaperone genes / negative regulation of retinoic acid receptor signaling pathway / complement component C1q complex binding / cellular response to electrical stimulus / intracellular glucocorticoid receptor signaling pathway / endoplasmic reticulum quality control compartment / sequestering of calcium ion / regulation of meiotic nuclear division / response to glycoside / sarcoplasmic reticulum lumen / protein folding in endoplasmic reticulum / hormone binding / disulfide oxidoreductase activity / nuclear export signal receptor activity / negative regulation of intracellular steroid hormone receptor signaling pathway / regulation of protein complex stability / cardiac muscle cell differentiation / molecular sequestering activity / phospholipase C activity / TAP1 binding / TAP2 binding / retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum / Scavenging by Class A Receptors / cellular response to interleukin-7 / positive regulation of extrinsic apoptotic signaling pathway / protein maturation by protein folding / Scavenging by Class F Receptors / cortical actin cytoskeleton organization / nuclear androgen receptor binding / response to testosterone / protein disulfide isomerase activity / cellular response to lithium ion / 小胞体 / T cell mediated cytotoxicity directed against tumor cell target / antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-dependent / positive regulation of memory T cell activation / TAP complex binding / protein localization to nucleus / antigen processing and presentation of exogenous peptide antigen via MHC class I / Golgi medial cisterna / negative regulation of neuron differentiation / protein-disulfide reductase activity / positive regulation of CD8-positive, alpha-beta T cell activation / CD8-positive, alpha-beta T cell activation / positive regulation of CD8-positive, alpha-beta T cell proliferation / CD8 receptor binding / MHC class I protein binding / endoplasmic reticulum exit site / beta-2-microglobulin binding / positive regulation of cell cycle / positive regulation of phagocytosis / phagocytic vesicle / : / positive regulation of substrate adhesion-dependent cell spreading / protein folding chaperone / TAP binding / extrinsic apoptotic signaling pathway / endocytic vesicle lumen / protection from natural killer cell mediated cytotoxicity / 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 / detection of bacterium / protein export from nucleus / endoplasmic reticulum-Golgi intermediate compartment membrane / response to endoplasmic reticulum stress / T cell receptor binding / positive regulation of endothelial cell migration / acrosomal vesicle / positive regulation of ferrous iron binding / positive regulation of transferrin receptor binding / early endosome lumen / positive regulation of receptor binding / Nef mediated downregulation of MHC class I complex cell surface expression / DAP12 interactions / negative regulation of receptor binding / lumenal side of endoplasmic reticulum membrane / Endosomal/Vacuolar pathway / Antigen Presentation: Folding, assembly and peptide loading of class I MHC / peptide binding / 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 / intracellular calcium ion homeostasis 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: 5.8 Å | |||||||||
データ登録者 | Trowitzsch, S. / Januliene, D. / Blees, A. / Moeller, A. / Tampe, R. | |||||||||
資金援助 | ドイツ, 2件
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引用 | ジャーナル: Nature / 年: 2017 タイトル: Structure of the human MHC-I peptide-loading complex. 著者: Andreas Blees / Dovile Januliene / Tommy Hofmann / Nicole Koller / Carla Schmidt / Simon Trowitzsch / Arne Moeller / Robert Tampé / 要旨: The peptide-loading complex (PLC) is a transient, multisubunit membrane complex in the endoplasmic reticulum that is essential for establishing a hierarchical immune response. The PLC coordinates ...The peptide-loading complex (PLC) is a transient, multisubunit membrane complex in the endoplasmic reticulum that is essential for establishing a hierarchical immune response. The PLC coordinates peptide translocation into the endoplasmic reticulum with loading and editing of major histocompatibility complex class I (MHC-I) molecules. After final proofreading in the PLC, stable peptide-MHC-I complexes are released to the cell surface to evoke a T-cell response against infected or malignant cells. Sampling of different MHC-I allomorphs requires the precise coordination of seven different subunits in a single macromolecular assembly, including the transporter associated with antigen processing (TAP1 and TAP2, jointly referred to as TAP), the oxidoreductase ERp57, the MHC-I heterodimer, and the chaperones tapasin and calreticulin. The molecular organization of and mechanistic events that take place in the PLC are unknown owing to the heterogeneous composition and intrinsically dynamic nature of the complex. Here, we isolate human PLC from Burkitt's lymphoma cells using an engineered viral inhibitor as bait and determine the structure of native PLC by electron cryo-microscopy. Two endoplasmic reticulum-resident editing modules composed of tapasin, calreticulin, ERp57, and MHC-I are centred around TAP in a pseudo-symmetric orientation. A multivalent chaperone network within and across the editing modules establishes the proofreading function at two lateral binding platforms for MHC-I molecules. The lectin-like domain of calreticulin senses the MHC-I glycan, whereas the P domain reaches over the MHC-I peptide-binding pocket towards ERp57. This arrangement allows tapasin to facilitate peptide editing by clamping MHC-I. The translocation pathway of TAP opens out into a large endoplasmic reticulum lumenal cavity, confined by the membrane entry points of tapasin and MHC-I. Two lateral windows channel the antigenic peptides to MHC-I. Structures of PLC captured at distinct assembly states provide mechanistic insight into the recruitment and release of MHC-I. Our work defines the molecular symbiosis of an ABC transporter and an endoplasmic reticulum chaperone network in MHC-I assembly and provides insight into the onset of the adaptive immune response. | |||||||||
履歴 |
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-構造の表示
ムービー |
ムービービューア |
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構造ビューア | 分子: MolmilJmol/JSmol |
-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 6eny.cif.gz | 250.5 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb6eny.ent.gz | 167.9 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 6eny.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/en/6eny ftp://data.pdbj.org/pub/pdb/validation_reports/en/6eny | HTTPS FTP |
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-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 , 5種, 5分子 BCDFG
#1: タンパク質 | 分子量: 11748.160 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) / 参照: UniProt: P61769 |
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#2: タンパク質 | 分子量: 45761.184 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) / 参照: UniProt: O15533 |
#3: タンパク質 | 分子量: 54341.102 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) 参照: UniProt: P30101, プロテインジスルフィドイソメラーゼ |
#4: タンパク質 | 分子量: 38363.535 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) / 参照: UniProt: P04439 |
#5: タンパク質 | 分子量: 46507.145 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) / 参照: UniProt: P27797 |
-糖 , 2種, 2分子
#6: 多糖 | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose |
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#7: 多糖 | beta-D-glucopyranose-(1-3)-alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose タイプ: oligosaccharideオリゴ糖 / 分子量: 666.578 Da / 分子数: 1 / 由来タイプ: 組換発現 |
-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: Protein Complexタンパク質複合体 / タイプ: COMPLEX / Entity ID: #1-#5 / 由来: NATURAL |
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分子量 | 実験値: NO |
由来(天然) | 生物種: Homo sapiens (ヒト) |
緩衝液 | pH: 7.5 |
試料 | 濃度: 2 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
試料支持 | グリッドのタイプ: C-flat-2/2 |
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 FIELDBright-field microscopy |
撮影 | 電子線照射量: 55 e/Å2 / 検出モード: COUNTING フィルム・検出器のモデル: GATAN K2 QUANTUM (4k x 4k) |
-解析
EMソフトウェア |
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CTF補正 | 詳細: CTF correction was performed internally in Relion and Frealign タイプ: NONE | ||||||||||||||||||||||||||||||||||||
対称性 | 点対称性: C1 (非対称) | ||||||||||||||||||||||||||||||||||||
3次元再構成 | 解像度: 5.8 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 141078 / 対称性のタイプ: POINT | ||||||||||||||||||||||||||||||||||||
精密化 | 最高解像度: 5.8 Å |