+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-14119 | |||||||||
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タイトル | Structure of the human MHC I peptide-loading complex editing module | |||||||||
マップデータ | ||||||||||
試料 |
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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 / TAP1 binding / TAP2 binding / cytolytic granule / protein disulfide-isomerase / 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 / TAP1 binding / TAP2 binding / cytolytic granule / protein disulfide-isomerase / positive regulation of dendritic cell chemotaxis / Assembly of Viral Components at the Budding Site / ATF6 (ATF6-alpha) activates chaperone genes / negative regulation of trophoblast cell migration / cortical granule / cellular response to electrical stimulus / nuclear receptor-mediated glucocorticoid signaling pathway / complement component C1q complex binding / regulation of meiotic nuclear division / negative regulation of retinoic acid receptor signaling pathway / response to glycoside / endoplasmic reticulum quality control compartment / sequestering of calcium ion / sarcoplasmic reticulum lumen / protein folding in endoplasmic reticulum / hormone binding / disulfide oxidoreductase activity / negative regulation of intracellular steroid hormone receptor signaling pathway / regulation of protein complex stability / nuclear export signal receptor activity / phospholipase C activity / cardiac muscle cell differentiation / molecular sequestering activity / retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum / positive regulation of extrinsic apoptotic signaling pathway / cellular response to interleukin-7 / Scavenging by Class A Receptors / protein maturation by protein folding / Scavenging by Class F Receptors / cortical actin cytoskeleton organization / positive regulation of memory T cell activation / T cell mediated cytotoxicity directed against tumor cell target / 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 / protein disulfide isomerase activity / MHC class I protein binding / antigen processing and presentation of exogenous peptide antigen via MHC class I / response to testosterone / endoplasmic reticulum exit site / antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-dependent / protein-disulfide reductase activity / TAP binding / protein localization to nucleus / protection from natural killer cell mediated cytotoxicity / negative regulation of neuron differentiation / smooth endoplasmic reticulum / positive regulation of cell cycle / beta-2-microglobulin binding / phagocytic vesicle / T cell receptor binding / detection of bacterium / positive regulation of substrate adhesion-dependent cell spreading / positive regulation of phagocytosis / ERAD pathway / extrinsic apoptotic signaling pathway / endocytic vesicle lumen / protein folding chaperone / endoplasmic reticulum-Golgi intermediate compartment membrane / response to endoplasmic reticulum stress / protein export from nucleus / positive regulation of endothelial cell migration / acrosomal vesicle / positive regulation of ferrous iron binding / positive regulation of transferrin receptor binding / negative regulation of receptor binding / DAP12 interactions / positive regulation of receptor binding / early endosome lumen / Nef mediated downregulation of MHC class I complex cell surface expression / platelet aggregation / antigen processing and presentation of endogenous peptide antigen via MHC class Ib / antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-independent / cellular response to iron ion / Endosomal/Vacuolar pathway / Antigen Presentation: Folding, assembly and peptide loading of class I MHC / lumenal side of endoplasmic reticulum membrane / 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 / 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 類似検索 - 分子機能 | |||||||||
生物種 | Homo sapiens (ヒト) / human (ヒト) | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.73 Å | |||||||||
データ登録者 | Domnick A / Susac L / Trowitzsch S / Thomas C / Tampe R | |||||||||
資金援助 | European Union, 2件
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引用 | ジャーナル: Nat Commun / 年: 2022 タイトル: Molecular basis of MHC I quality control in the peptide loading complex. 著者: Alexander Domnick / Christian Winter / Lukas Sušac / Leon Hennecke / Mario Hensen / Nicole Zitzmann / Simon Trowitzsch / Christoph Thomas / Robert Tampé / 要旨: Major histocompatibility complex class I (MHC I) molecules are central to adaptive immunity. Their assembly, epitope selection, and antigen presentation are controlled by the MHC I glycan through a ...Major histocompatibility complex class I (MHC I) molecules are central to adaptive immunity. Their assembly, epitope selection, and antigen presentation are controlled by the MHC I glycan through a sophisticated network of chaperones and modifying enzymes. However, the mechanistic integration of the corresponding processes remains poorly understood. Here, we determine the multi-chaperone-client interaction network of the peptide loading complex (PLC) and report the PLC editing module structure by cryogenic electron microscopy at 3.7 Å resolution. Combined with epitope-proofreading studies of the PLC in near-native lipid environment, these data show that peptide-receptive MHC I molecules are stabilized by multivalent chaperone interactions including the calreticulin-engulfed mono-glucosylated MHC I glycan, which only becomes accessible for processing by α-glucosidase II upon loading of optimal epitopes. Our work reveals allosteric coupling between peptide-MHC I assembly and glycan processing. This inter-process communication defines the onset of an adaptive immune response and provides a prototypical example of the tightly coordinated events in endoplasmic reticulum quality control. | |||||||||
履歴 |
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-構造の表示
添付画像 |
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-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_14119.map.gz | 166.7 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-14119-v30.xml emd-14119.xml | 14.2 KB 14.2 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_14119.png | 70.6 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-14119 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-14119 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_14119_validation.pdf.gz | 358.6 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_14119_full_validation.pdf.gz | 358.1 KB | 表示 | |
XML形式データ | emd_14119_validation.xml.gz | 6.7 KB | 表示 | |
CIF形式データ | emd_14119_validation.cif.gz | 7.7 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-14119 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-14119 | HTTPS FTP |
-関連構造データ
関連構造データ | 7qpdMC M: このマップから作成された原子モデル C: 同じ文献を引用 (文献) |
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類似構造データ | 類似検索 - 機能・相同性F&H 検索 |
-リンク
EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
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「今月の分子」の関連する項目 |
-マップ
ファイル | ダウンロード / ファイル: emd_14119.map.gz / 形式: CCP4 / 大きさ: 178 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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投影像・断面図 | 画像のコントロール
画像は Spider により作成 | ||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.05 Å | ||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
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-添付データ
-試料の構成要素
-全体 : editing module of peptide-loading complex
全体 | 名称: editing module of peptide-loading complex |
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要素 |
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-超分子 #1: editing module of peptide-loading complex
超分子 | 名称: editing module of peptide-loading complex / タイプ: complex / キメラ: Yes / ID: 1 / 親要素: 0 / 含まれる分子: all |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
-分子 #1: Beta-2-microglobulin
分子 | 名称: Beta-2-microglobulin / タイプ: protein_or_peptide / ID: 1 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: human (ヒト) |
分子量 | 理論値: 11.74816 KDa |
配列 | 文字列: IQRTPKIQVY SRHPAENGKS NFLNCYVSGF HPSDIEVDLL KNGERIEKVE HSDLSFSKDW SFYLLYYTEF TPTEKDEYAC RVNHVTLSQ PKIVKWDRDM |
-分子 #2: Tapasin
分子 | 名称: Tapasin / タイプ: protein_or_peptide / ID: 2 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: human (ヒト) |
分子量 | 理論値: 45.761184 KDa |
配列 | 文字列: GPAVIECWFV EDASGKGLAK RPGALLLRQG PGEPPPRPDL DPELYLSVHD PAGALQAAFR RYPRGAPAPH CEMSRFVPLP ASAKWASGL TPAQNCPRAL DGAWLMVSIS SPVLSLSSLL RPQPEPQQEP VLITMATVVL TVLTHTPAPR VRLGQDALLD L SFAYMPPT ...文字列: GPAVIECWFV EDASGKGLAK RPGALLLRQG PGEPPPRPDL DPELYLSVHD PAGALQAAFR RYPRGAPAPH CEMSRFVPLP ASAKWASGL TPAQNCPRAL DGAWLMVSIS SPVLSLSSLL RPQPEPQQEP VLITMATVVL TVLTHTPAPR VRLGQDALLD L SFAYMPPT SEAASSLAPG PPPFGLEWRR QHLGKGHLLL AATPGLNGQM PAAQEGAVAF AAWDDDEPWG PWTGNGTFWL PR VQPFQEG TYLATIHLPY LQGQVTLELA VYKPPKVSLM PATLARAAPG EAPPELLCLV SHFYPSGGLE VEWELRGGPG GRS QKAEGQ RWLSALRHHS DGSVSLSGHL QPPPVTTEQH GARYACRIHH PSLPASGRSA EVTLEVAGLS GPSLEDSVGL FLSA FLLLG LFKALGWAAV YLSTCKDSKK KAE |
-分子 #3: Protein disulfide-isomerase A3
分子 | 名称: Protein disulfide-isomerase A3 / タイプ: protein_or_peptide / ID: 3 / コピー数: 1 / 光学異性体: LEVO / EC番号: protein disulfide-isomerase |
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由来(天然) | 生物種: human (ヒト) |
分子量 | 理論値: 54.341102 KDa |
配列 | 文字列: SDVLELTDDN FESRISDTGS AGLMLVEFFA PWCGHCKRLA PEYEAAATRL KGIVPLAKVD CTANTNTCNK YGVSGYPTLK IFRDGEEAG AYDGPRTADG IVSHLKKQAG PASVPLRTEE EFKKFISDKD ASIVGFFDDS FSEAHSEFLK AASNLRDNYR F AHTNVESL ...文字列: SDVLELTDDN FESRISDTGS AGLMLVEFFA PWCGHCKRLA PEYEAAATRL KGIVPLAKVD CTANTNTCNK YGVSGYPTLK IFRDGEEAG AYDGPRTADG IVSHLKKQAG PASVPLRTEE EFKKFISDKD ASIVGFFDDS FSEAHSEFLK AASNLRDNYR F AHTNVESL VNEYDDNGEG IILFRPSHLT NKFEDKTVAY TEQKMTSGKI KKFIQENIFG ICPHMTEDNK DLIQGKDLLI AY YDVDYEK NAKGSNYWRN RVMMVAKKFL DAGHKLNFAV ASRKTFSHEL SDFGLESTAG EIPVVAIRTA KGEKFVMQEE FSR DGKALE RFLQDYFDGN LKRYLKSEPI PESNDGPVKV VVAENFDEIV NNENKDVLIE FYAPWCGHCK NLEPKYKELG EKLS KDPNI VIAKMDATAN DVPSPYEVRG FPTIYFSPAN KKLNPKKYEG GRELSDFISY LQREATNPPV IQEEKPKKKK KAQED L |
-分子 #4: HLA class I histocompatibility antigen, A-3 alpha chain
分子 | 名称: HLA class I histocompatibility antigen, A-3 alpha chain タイプ: protein_or_peptide / ID: 4 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: human (ヒト) |
分子量 | 理論値: 38.363535 KDa |
配列 | 文字列: GSHSMRYFFT SVSRPGRGEP RFIAVGYVDD TQFVRFDSDA ASQRMEPRAP WIEQEGPEYW DQETRNVKAQ SQTDRVDLGT LRGYYNQSE AGSHTIQIMY GCDVGSDGRF LRGYRQDAYD GKDYIALNED LRSWTAADMA AQITKRKWEA AHEAEQLRAY L DGTCVEWL ...文字列: GSHSMRYFFT SVSRPGRGEP RFIAVGYVDD TQFVRFDSDA ASQRMEPRAP WIEQEGPEYW DQETRNVKAQ SQTDRVDLGT LRGYYNQSE AGSHTIQIMY GCDVGSDGRF LRGYRQDAYD GKDYIALNED LRSWTAADMA AQITKRKWEA AHEAEQLRAY L DGTCVEWL RRYLENGKET LQRTDPPKTH MTHHPISDHE ATLRCWALGF YPAEITLTWQ RDGEDQTQDT ELVETRPAGD GT FQKWAAV VVPSGEEQRY TCHVQHEGLP KPLTLRWELS SQPTIPIVGI IAGLVLLGAV ITGAVVAAVM WRRKSSDRKG GSY TQAASS DSAQGSDVSL TACKV |
-分子 #5: Calreticulin
分子 | 名称: Calreticulin / タイプ: protein_or_peptide / ID: 5 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: human (ヒト) |
分子量 | 理論値: 46.523211 KDa |
配列 | 文字列: EPAVYFKEQF LDGDGWTSRW IESKHKSDFG KFVLSSGKFY GDEEKDKGLQ TSQDARFYAL SASFEPFSNK GQTLVVQFTV KHEQNIDCG GGYVKLFPNS LDQTDMHGDS EYNIMFGPDI CGPGTKKVHV IFNYKGKNVL INKDIRCKDD EFTHLYTLIV R PDNTYEVK ...文字列: EPAVYFKEQF LDGDGWTSRW IESKHKSDFG KFVLSSGKFY GDEEKDKGLQ TSQDARFYAL SASFEPFSNK GQTLVVQFTV KHEQNIDCG GGYVKLFPNS LDQTDMHGDS EYNIMFGPDI CGPGTKKVHV IFNYKGKNVL INKDIRCKDD EFTHLYTLIV R PDNTYEVK IDNSQVESGS LEDDWDFLPP KKIKDPDASK PEDWDERAKI DDPTDSKPED WDKPEHIPDP DAKKPEDWDE EM DGEWEPP VIQNPEYKGE WKPRQIDNPD YKGTWIHPEI DNPEYSPDPS IYAYDNFGVL GLDLWQVKSG TIFDNFLITN DEA YAEEFG NETWGVTKAA EKQMKDKQDE EQRLKEEEED KKRKEEEEAE DKEDDEDKDE DEEDEEDKEE DEEEDVPGQA KDEL |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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解析 | 単粒子再構成法 |
試料の集合状態 | particle |
-試料調製
緩衝液 | pH: 7.4 |
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凍結 | 凍結剤: ETHANE |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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撮影 | フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) 平均電子線量: 68.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 2.5 µm / 最小 デフォーカス(公称値): 1.0 µm |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
-画像解析
CTF補正 | 詳細: Patch CTF |
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最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 3.73 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 97952 |
初期 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |