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データを開く
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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 | ||||||||||||
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![]() | IMMUNE SYSTEM / adaptive immunity / antigen processing / chaperone / MHC class I | ||||||||||||
機能・相同性 | ![]() MHC class Ib protein complex assembly / peptide antigen stabilization / Tapasin-ERp57 complex / Calnexin/calreticulin cycle / MHC class I protein complex binding / TAP1 binding / TAP2 binding / cytolytic granule / positive regulation of dendritic cell chemotaxis / protein disulfide-isomerase ...MHC class Ib protein complex assembly / peptide antigen stabilization / Tapasin-ERp57 complex / Calnexin/calreticulin cycle / MHC class I protein complex binding / TAP1 binding / TAP2 binding / cytolytic granule / positive regulation of dendritic cell chemotaxis / protein disulfide-isomerase / cortical granule / Assembly of Viral Components at the Budding Site / negative regulation of trophoblast cell migration / ATF6 (ATF6-alpha) activates chaperone genes / negative regulation of retinoic acid receptor signaling pathway / cellular response to electrical stimulus / endoplasmic reticulum quality control compartment / nuclear receptor-mediated glucocorticoid signaling pathway / regulation of meiotic nuclear division / complement component C1q complex binding / sequestering of calcium ion / response to glycoside / sarcoplasmic reticulum lumen / disulfide oxidoreductase activity / protein folding in endoplasmic reticulum / nuclear export signal receptor activity / negative regulation of intracellular steroid hormone receptor signaling pathway / regulation of protein complex stability / hormone binding / cardiac muscle cell differentiation / molecular sequestering activity / phospholipase C activity / retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum / positive regulation of extrinsic apoptotic signaling pathway / cellular response to interleukin-7 / protein maturation by protein folding / Scavenging by Class F Receptors / Scavenging by Class A Receptors / cortical actin cytoskeleton organization / T cell mediated cytotoxicity directed against tumor cell target / positive regulation of memory T cell activation / TAP complex binding / nuclear androgen receptor binding / positive regulation of CD8-positive, alpha-beta T cell activation / CD8-positive, alpha-beta T cell activation / Golgi medial cisterna / positive regulation of CD8-positive, alpha-beta T cell proliferation / cellular response to lithium ion / CD8 receptor binding / response to testosterone / protein disulfide isomerase activity / MHC class I protein binding / antigen processing and presentation of exogenous peptide antigen via MHC class I / endoplasmic reticulum exit site / antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-dependent / TAP binding / protein localization to nucleus / protection from natural killer cell mediated cytotoxicity / negative regulation of neuron differentiation / protein-disulfide reductase activity / smooth endoplasmic reticulum / beta-2-microglobulin binding / T cell receptor binding / positive regulation of cell cycle / detection of bacterium / ERAD pathway / extrinsic apoptotic signaling pathway / positive regulation of substrate adhesion-dependent cell spreading / protein folding chaperone / positive regulation of phagocytosis / endocytic vesicle lumen / protein export from nucleus / phagocytic vesicle / positive regulation of endothelial cell migration / endoplasmic reticulum-Golgi intermediate compartment membrane / response to endoplasmic reticulum stress / acrosomal vesicle / 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 / lumenal side of endoplasmic reticulum membrane / cellular response to iron ion / Endosomal/Vacuolar pathway / Antigen Presentation: Folding, assembly and peptide loading of class I MHC / peptide binding / cellular response to iron(III) ion / 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 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: 5.8 Å | ||||||||||||
![]() | Trowitzsch, S. / Januliene, D. / Blees, A. / Moeller, A. / Tampe, R. | ||||||||||||
資金援助 | ![]()
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![]() | ![]() 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 |
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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 | ![]() | 257.1 KB | 表示 | ![]() |
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PDB形式 | ![]() | 168 KB | 表示 | ![]() |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
その他 | ![]() |
-検証レポート
文書・要旨 | ![]() | 952.6 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 967.9 KB | 表示 | |
XML形式データ | ![]() | 40.3 KB | 表示 | |
CIF形式データ | ![]() | 63.5 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
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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
-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) ![]() |
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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) ![]() |
#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) ![]() |
#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) ![]() |
#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) ![]() |
-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 / 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 |
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試料調製
構成要素 | 名称: Protein Complex / 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: ![]() |
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 |
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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 |
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) |
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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 |