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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: 9rcv | ||||||||||||||||||
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| タイトル | Structure of the Human Peptide-Loading Complex Arrested by HCMV US6 | ||||||||||||||||||
要素 |
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キーワード | IMMUNE SYSTEM / antigen processing / adaptive immunity / cryo-EM / ER chaperones / MHC class I / transporter associated with antigen processing | ||||||||||||||||||
| 機能・相同性 | 機能・相同性情報MHC class Ib protein complex assembly / peptide antigen stabilization / Tapasin-ERp57 complex / MHC class I protein complex binding / antigen processing and presentation of endogenous peptide antigen via MHC class Ib via ER pathway, TAP-dependent / tapasin binding / ABC-type peptide antigen transporter activity / ABC-type antigen peptide transporter / TAP complex / ABC-type peptide transporter activity ...MHC class Ib protein complex assembly / peptide antigen stabilization / Tapasin-ERp57 complex / MHC class I protein complex binding / antigen processing and presentation of endogenous peptide antigen via MHC class Ib via ER pathway, TAP-dependent / tapasin binding / ABC-type peptide antigen transporter activity / ABC-type antigen peptide transporter / TAP complex / ABC-type peptide transporter activity / antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent / peptide antigen transport / MHC class Ib protein binding / cytosol to endoplasmic reticulum transport / symbiont-mediated suppression of host antigen processing and presentation of peptide antigen via MHC class I / TAP2 binding / TAP1 binding / regulation of protein complex stability / retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum / peptide transport / peptide transmembrane transporter activity / antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-dependent / TAP complex binding / MHC class I protein binding / molecular sequestering activity / antigen processing and presentation of peptide antigen via MHC class I / endoplasmic reticulum-Golgi intermediate compartment membrane / protein folding chaperone / early endosome lumen / Nef mediated downregulation of MHC class I complex cell surface expression / DAP12 interactions / Endosomal/Vacuolar pathway / T cell mediated cytotoxicity / Antigen Presentation: Folding, assembly and peptide loading of class I MHC / lumenal side of endoplasmic reticulum membrane / regulation of iron ion transport / cellular response to iron(III) ion / negative regulation of iron ion transport / negative regulation of forebrain neuron differentiation / antigen processing and presentation of exogenous protein antigen via MHC class Ib, TAP-dependent / ER to Golgi transport vesicle membrane / peptide antigen assembly with MHC class I protein complex / regulation of erythrocyte differentiation / response to molecule of bacterial origin / HFE-transferrin receptor complex / defense response / transferrin transport / MHC class I peptide loading complex / cellular response to iron ion / negative regulation of receptor-mediated endocytosis / positive regulation of T cell cytokine production / antigen processing and presentation of endogenous peptide antigen via MHC class I / MHC class I protein complex / ADP binding / peptide antigen assembly with MHC class II protein complex / negative regulation of neurogenesis / cellular response to nicotine / MHC class II protein complex / positive regulation of receptor-mediated endocytosis / multicellular organismal-level iron ion homeostasis / positive regulation of T cell mediated cytotoxicity / transmembrane transport / specific granule lumen / positive regulation of immune response / antigen processing and presentation of exogenous peptide antigen via MHC class II / peptide antigen binding / phagocytic vesicle membrane / recycling endosome membrane / centriolar satellite / positive regulation of T cell activation / negative regulation of epithelial cell proliferation / Interferon gamma signaling / Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell / Modulation by Mtb of host immune system / positive regulation of cellular senescence / sensory perception of smell / tertiary granule lumen / : / MHC class II protein complex binding / DAP12 signaling / T cell differentiation in thymus / late endosome membrane / protein transport / negative regulation of neuron projection development / ER-Phagosome pathway / protein refolding / regulation of gene expression / protein-containing complex assembly / early endosome membrane / molecular adaptor activity / amyloid fibril formation / protein homotetramerization / intracellular iron ion homeostasis / adaptive immune response / learning or memory / nuclear speck / immune response / host cell endoplasmic reticulum membrane / endoplasmic reticulum lumen / Amyloid fiber formation 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: 2.7 Å | ||||||||||||||||||
データ登録者 | Stolz, M. / Susac, L. / Trowitzsch, S. / Tampe, R. | ||||||||||||||||||
| 資金援助 | European Union, ドイツ, 米国, 5件
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引用 | ジャーナル: Sci Adv / 年: 2026タイトル: Architectural principles of transporter-chaperone coupling within the native MHC I peptide-loading complex. 著者: Milena Stolz / Lukas Sušac / Amin Fahim / Rieke Keller / Lisa Saggau / Filippo Mancia / Simon Trowitzsch / Robert Tampé / ![]() 要旨: Adaptive immunity depends on major histocompatibility complex class I (MHC I) presentation of peptides, a process orchestrated by the peptide-loading complex (PLC) in the endoplasmic reticulum (ER). ...Adaptive immunity depends on major histocompatibility complex class I (MHC I) presentation of peptides, a process orchestrated by the peptide-loading complex (PLC) in the endoplasmic reticulum (ER). The PLC ensures precise peptide selection and loading and is a major target of viral immune evasion, notably by human cytomegalovirus (HCMV). Here, we report the 2.59- to 2.88-Å cryo-electron microscopy structure of native human PLC bound to the HCMV immune evasin US6. US6 inhibits the transporter associated with antigen processing 1/2 (TAP1/2) by laterally attaching its transmembrane helix to TAP2 using a disulfide-rich domain to mimic a translocating peptide. This domain blocks the ER-lumenal exit and locks TAP in an outward-facing conformation with closed nucleotide-binding domains and asymmetric adenosine 5'-triphosphate/adenosine 5'-diphosphate occlusion. The structure also reveals how TAP's amino-terminal transmembrane domains scaffold the MHC I chaperone tapasin. These findings elucidate the mechanism of US6-mediated immune evasion and highlight potential targets for therapeutic modulation of immune presentation in infection and cancer. #1: ジャーナル: Acta Crystallogr D Struct Biol / 年: 2019 タイトル: Macromolecular structure determination using X-rays, neutrons and electrons: recent developments in Phenix. 著者: Dorothee Liebschner / Pavel V Afonine / Matthew L Baker / Gábor Bunkóczi / Vincent B Chen / Tristan I Croll / Bradley Hintze / Li Wei Hung / Swati Jain / Airlie J McCoy / Nigel W Moriarty / ...著者: Dorothee Liebschner / Pavel V Afonine / Matthew L Baker / Gábor Bunkóczi / Vincent B Chen / Tristan I Croll / Bradley Hintze / Li Wei Hung / Swati Jain / Airlie J McCoy / Nigel W Moriarty / Robert D Oeffner / Billy K Poon / Michael G Prisant / Randy J Read / Jane S Richardson / David C Richardson / Massimo D Sammito / Oleg V Sobolev / Duncan H Stockwell / Thomas C Terwilliger / Alexandre G Urzhumtsev / Lizbeth L Videau / Christopher J Williams / Paul D Adams / ![]() 要旨: Diffraction (X-ray, neutron and electron) and electron cryo-microscopy are powerful methods to determine three-dimensional macromolecular structures, which are required to understand biological ...Diffraction (X-ray, neutron and electron) and electron cryo-microscopy are powerful methods to determine three-dimensional macromolecular structures, which are required to understand biological processes and to develop new therapeutics against diseases. The overall structure-solution workflow is similar for these techniques, but nuances exist because the properties of the reduced experimental data are different. Software tools for structure determination should therefore be tailored for each method. Phenix is a comprehensive software package for macromolecular structure determination that handles data from any of these techniques. Tasks performed with Phenix include data-quality assessment, map improvement, model building, the validation/rebuilding/refinement cycle and deposition. Each tool caters to the type of experimental data. The design of Phenix emphasizes the automation of procedures, where possible, to minimize repetitive and time-consuming manual tasks, while default parameters are chosen to encourage best practice. A graphical user interface provides access to many command-line features of Phenix and streamlines the transition between programs, project tracking and re-running of previous tasks. | ||||||||||||||||||
| 履歴 |
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構造の表示
| 構造ビューア | 分子: Molmil Jmol/JSmol |
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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 | 9rcv.cif.gz | 610.3 KB | 表示 | PDBx/mmCIF形式 |
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| PDB形式 | pdb9rcv.ent.gz | 478.5 KB | 表示 | PDB形式 |
| PDBx/mmJSON形式 | 9rcv.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/rc/9rcv ftp://data.pdbj.org/pub/pdb/validation_reports/rc/9rcv | HTTPS FTP |
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-関連構造データ
| 関連構造データ | ![]() 53923MC C: 同じ文献を引用 ( M: このデータのモデリングに利用したマップデータ |
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| 類似構造データ | 類似検索 - 機能・相同性 F&H 検索 |
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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
-Antigen peptide transporter ... , 2種, 2分子 AE
| #1: タンパク質 | 分子量: 81080.383 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) / 細胞株: Raji / 組織: Burkitt lymphoma参照: UniProt: Q03518, ABC-type antigen peptide transporter |
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| #5: タンパク質 | 分子量: 74697.242 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) / 細胞株: Raji / 組織: Burkitt lymphoma参照: UniProt: Q03519, ABC-type antigen peptide transporter |
-タンパク質 , 4種, 7分子 BFCGDHI
| #2: タンパク質 | 分子量: 47673.539 Da / 分子数: 2 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) / 細胞株: Raji / 組織: Burkitt lymphoma / 参照: UniProt: O15533#3: タンパク質 | 分子量: 40480.973 Da / 分子数: 2 / 由来タイプ: 天然 / 詳細: HLA-B*15:10 / 由来: (天然) Homo sapiens (ヒト) / 細胞株: Raji / 組織: Burkitt lymphoma / 参照: UniProt: A0A678ZHF8#4: タンパク質 | 分子量: 13732.547 Da / 分子数: 2 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) / 細胞株: Raji / 組織: Burkitt lymphoma / 参照: UniProt: P61769#6: タンパク質 | | 分子量: 20671.127 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: US6 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P14334 |
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-糖 , 2種, 4分子 
| #7: 多糖 | | #10: 糖 | |
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-非ポリマー , 4種, 8分子 






| #8: 化合物 | ChemComp-ATP / | ||||
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| #9: 化合物 | | #11: 化合物 | ChemComp-ADP / | #12: 水 | ChemComp-HOH / | |
-詳細
| 研究の焦点であるリガンドがあるか | Y |
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| Has protein modification | Y |
-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: Human peptide-loading complex arrested by HCMV US6 / タイプ: COMPLEX / Entity ID: #1-#6 / 由来: NATURAL | ||||||||||||||||||||||||||||||
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| 分子量 |
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| 由来(天然) | 生物種: Homo sapiens (ヒト) | ||||||||||||||||||||||||||||||
| 緩衝液 | pH: 6.5 詳細: 20 mM HEPES-NaOH pH 6.5, 150 mM NaCl, 10 mM MgCl2, 2.5 mM biotin, 0.05% (w/v) glycodiosgenin | ||||||||||||||||||||||||||||||
| 緩衝液成分 |
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| 試料 | 濃度: 3.5 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: GOLD / グリッドのサイズ: 300 divisions/in. / グリッドのタイプ: UltrAuFoil | ||||||||||||||||||||||||||||||
| 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 / 詳細: Blot force 5, Blot time 5 s |
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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: TFS 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): 105000 X / 倍率(補正後): 60241 X / 最大 デフォーカス(公称値): 1500 nm / 最小 デフォーカス(公称値): 500 nm / Cs: 2.7 mm |
| 試料ホルダ | 凍結剤: NITROGEN 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER |
| 撮影 | 電子線照射量: 58 e/Å2 / フィルム・検出器のモデル: GATAN K3 (6k x 4k) / 撮影したグリッド数: 3 / 実像数: 25454 |
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解析
| EMソフトウェア | 名称: PHENIX / カテゴリ: モデル精密化 |
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| CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION |
| 粒子像の選択 | 選択した粒子像数: 726723 |
| 対称性 | 点対称性: C1 (非対称) |
| 3次元再構成 | 解像度: 2.7 Å / 解像度の算出法: OTHER / 粒子像の数: 269213 詳細: Composite map generated from 4 focus maps ranging 2.59 - 2.88 A 対称性のタイプ: POINT |
| 精密化 | 交差検証法: NONE |
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万見について




Homo sapiens (ヒト)
ドイツ,
米国, 5件
引用







PDBj




gel filtration
