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基本情報
登録情報 | ![]() | ||||||||||||
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タイトル | Human E3 ligase E6AP in complex with HPV16-E6 and p53 | ||||||||||||
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![]() | Complex / Viral / Ubiquitination / LIGASE | ||||||||||||
機能・相同性 | ![]() sperm entry / positive regulation of Golgi lumen acidification / symbiont-mediated suppression of host transcription / regulation of ubiquitin-dependent protein catabolic process / symbiont-mediated suppression of host apoptosis / prostate gland growth / HECT-type E3 ubiquitin transferase / negative regulation of helicase activity / Loss of function of TP53 in cancer due to loss of tetramerization ability / Regulation of TP53 Expression ...sperm entry / positive regulation of Golgi lumen acidification / symbiont-mediated suppression of host transcription / regulation of ubiquitin-dependent protein catabolic process / symbiont-mediated suppression of host apoptosis / prostate gland growth / HECT-type E3 ubiquitin transferase / negative regulation of helicase activity / Loss of function of TP53 in cancer due to loss of tetramerization ability / Regulation of TP53 Expression / signal transduction by p53 class mediator / negative regulation of G1 to G0 transition / negative regulation of glucose catabolic process to lactate via pyruvate / Transcriptional activation of cell cycle inhibitor p21 / regulation of intrinsic apoptotic signaling pathway by p53 class mediator / negative regulation of pentose-phosphate shunt / ATP-dependent DNA/DNA annealing activity / Activation of NOXA and translocation to mitochondria / regulation of cell cycle G2/M phase transition / regulation of fibroblast apoptotic process / intrinsic apoptotic signaling pathway in response to hypoxia / oligodendrocyte apoptotic process / negative regulation of miRNA processing / positive regulation of thymocyte apoptotic process / oxidative stress-induced premature senescence / regulation of tissue remodeling / positive regulation of mitochondrial membrane permeability / regulation of Cdc42 protein signal transduction / mRNA transcription / positive regulation of programmed necrotic cell death / bone marrow development / circadian behavior / T cell proliferation involved in immune response / regulation of mitochondrial membrane permeability involved in apoptotic process / germ cell nucleus / RUNX3 regulates CDKN1A transcription / IgG binding / glucose catabolic process to lactate via pyruvate / TP53 Regulates Transcription of Death Receptors and Ligands / TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain / Activation of PUMA and translocation to mitochondria / regulation of DNA damage response, signal transduction by p53 class mediator / histone deacetylase regulator activity / negative regulation of glial cell proliferation / Regulation of TP53 Activity through Association with Co-factors / negative regulation of neuroblast proliferation / mitochondrial DNA repair / T cell lineage commitment / Formation of Senescence-Associated Heterochromatin Foci (SAHF) / ER overload response / thymocyte apoptotic process / B cell lineage commitment / TP53 Regulates Transcription of Caspase Activators and Caspases / negative regulation of mitophagy / androgen receptor signaling pathway / cardiac septum morphogenesis / negative regulation of DNA replication / entrainment of circadian clock by photoperiod / PI5P Regulates TP53 Acetylation / negative regulation of telomere maintenance via telomerase / Zygotic genome activation (ZGA) / positive regulation of release of cytochrome c from mitochondria / Association of TriC/CCT with target proteins during biosynthesis / necroptotic process / TP53 Regulates Transcription of Genes Involved in Cytochrome C Release / TFIID-class transcription factor complex binding / SUMOylation of transcription factors / TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain / intrinsic apoptotic signaling pathway by p53 class mediator / negative regulation of reactive oxygen species metabolic process / rRNA transcription / Transcriptional Regulation by VENTX / regulation of proteolysis / replicative senescence / general transcription initiation factor binding / cellular response to UV-C / progesterone receptor signaling pathway / cellular response to actinomycin D / intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress / positive regulation of execution phase of apoptosis / positive regulation of RNA polymerase II transcription preinitiation complex assembly / neuroblast proliferation / intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / response to X-ray / hematopoietic stem cell differentiation / Pyroptosis / viral process / postsynaptic cytosol / embryonic organ development / chromosome organization / type II interferon-mediated signaling pathway / TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest / somitogenesis / hematopoietic progenitor cell differentiation / glial cell proliferation / protein K48-linked ubiquitination / negative regulation of fibroblast proliferation / core promoter sequence-specific DNA binding / positive regulation of cardiac muscle cell apoptotic process / negative regulation of stem cell proliferation 類似検索 - 分子機能 | ||||||||||||
生物種 | ![]() ![]() | ||||||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.54 Å | ||||||||||||
![]() | Kenny S / Das C | ||||||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Structure of E6AP in complex with HPV16-E6 and p53 reveals a novel ordered domain important for E3 ligase activation. 著者: Sebastian Kenny / Shalini Iyer / Clinton A Gabel / Natalia Tegenfeldt / Andrew G DeMarco / Mark C Hall / Leifu Chang / V Jo Davisson / Scott Vande Pol / Chittaranjan Das / ![]() 要旨: High-risk human papillomavirus E6 oncoprotein is a model system for the recognition and degradation of cellular p53 tumor suppressor protein. There remains a gap in the understanding of the ubiquitin ...High-risk human papillomavirus E6 oncoprotein is a model system for the recognition and degradation of cellular p53 tumor suppressor protein. There remains a gap in the understanding of the ubiquitin transfer reaction, including placement of the E6AP catalytic HECT domain of the ligase concerning the p53 substrate and how E6 itself is protected from ubiquitination. We determined the cryoelectron microscopy (cryo-EM) structure of the E6AP/E6/p53 complex, related the structure to in vivo modeling of the tri-molecular complex, and identified structural interactions associated with activation of the ubiquitin ligase function. The structure reveals that the N-terminal ordered domain (NOD) in E6AP has a terminal alpha helix that mediates the interaction of the NOD with the HECT domain of E6AP and protects the HPV-E6 protein from ubiquitination. In addition, this NOD helix is required for E6AP ligase function by contributing to the affinity of the E6-E6AP association, modulating E6 substrate recognition, while displacing UbcH7. | ||||||||||||
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 | ![]() | 59.7 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 21.7 KB 21.7 KB | 表示 表示 | ![]() |
画像 | ![]() | 34.2 KB | ||
Filedesc metadata | ![]() | 7.2 KB | ||
その他 | ![]() ![]() | 59.3 MB 59.3 MB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-検証レポート
文書・要旨 | ![]() | 730.6 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 730.1 KB | 表示 | |
XML形式データ | ![]() | 12.2 KB | 表示 | |
CIF形式データ | ![]() | 14.4 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
関連構造データ | ![]() 9chtMC 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 ( |
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類似構造データ | 類似検索 - 機能・相同性 ![]() |
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リンク
EMDBのページ | ![]() ![]() |
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「今月の分子」の関連する項目 |
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マップ
ファイル | ![]() | ||||||||||||||||||||||||||||||||||||
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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: 0.86 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
-ハーフマップ: #2
ファイル | emd_45601_half_map_1.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: #1
ファイル | emd_45601_half_map_2.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
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試料の構成要素
-全体 : Ternary complex of E6AP with viral factor E6 and neosubstrate p53
全体 | 名称: Ternary complex of E6AP with viral factor E6 and neosubstrate p53 |
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要素 |
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-超分子 #1: Ternary complex of E6AP with viral factor E6 and neosubstrate p53
超分子 | 名称: Ternary complex of E6AP with viral factor E6 and neosubstrate p53 タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: all |
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由来(天然) | 生物種: ![]() |
-分子 #1: Ubiquitin-protein ligase E3A
分子 | 名称: Ubiquitin-protein ligase E3A / タイプ: protein_or_peptide / ID: 1 / コピー数: 1 / 光学異性体: LEVO / EC番号: HECT-type E3 ubiquitin transferase |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 102.982867 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MGSSHHHHHH SSGLVPRGSH MEKLHQCYWK SGEPQSDDIE ASRMKRAAAK HLIERYYHQL TEGCGNEACT NEFCASCPTF LRMDNNAAA IKALELYKIN AKLCDPHPSK KGASSAYLEN SKGAPNNSCS EIKMNKKGAR IDFKDVTYLT EEKVYEILEL C REREDYSP ...文字列: MGSSHHHHHH SSGLVPRGSH MEKLHQCYWK SGEPQSDDIE ASRMKRAAAK HLIERYYHQL TEGCGNEACT NEFCASCPTF LRMDNNAAA IKALELYKIN AKLCDPHPSK KGASSAYLEN SKGAPNNSCS EIKMNKKGAR IDFKDVTYLT EEKVYEILEL C REREDYSP LIRVIGRVFS SAEALVQSFR KVKQHTKEEL KSLQAKDEDK DEDEKEKAAC SAAAMEEDSE ASSSRIGDSS QG DNNLQKL GPDDVSVDID AIRRVYTRLL SNEKIETAFL NALVYLSPNV ECDLTYHNVY SRDPNYLNLF IIVMENRNLH SPE YLEMAL PLFCKAMSKL PLAAQGKLIR LWSKYNADQI RRMMETFQQL ITYKVISNEF NSRNLVNDDD AIVAASKCLK MVYY ANVVG GEVDTNHNEE DDEEPIPESS ELTLQELLGE ERRNKKGPRV DPLETELGVK TLDCRKPLIP FEEFINEPLN EVLEM DKDY TFFKVETENK FSFMTCPFIL NAVTKNLGLY YDNRIRMYSE RRITVLYSLV QGQQLNPYLR LKVRRDHIID DALVRL EMI AMENPADLKK QLYVEFEGEQ GVDEGGVSKE FFQLVVEEIF NPDIGMFTYD ESTKLFWFNP SSFETEGQFT LIGIVLG LA IYNNCILDVH FPMVVYRKLM GKKGTFRDLG DSHPVLYQSL KDLLEYEGNV EDDMMITFQI SQTDLFGNPM MYDLKENG D KIPITNENRK EFVNLYSDYI LNKSVEKQFK AFRRGFHMVT NESPLKYLFR PEEIELLICG SRNLDFQALE ETTEYDGGY TRDSVLIREF WEIVHSFTDE QKRLFLQFTT GTDRAPVGGL GKLKMIIAKN GPDTERLPTS HTCFNVLLLP EYSSKEKLKE RLLKAITYA KGFGML UniProtKB: Ubiquitin-protein ligase E3A |
-分子 #2: Immunoglobulin G-binding protein G/Cellular tumor antigen p53 fus...
分子 | 名称: Immunoglobulin G-binding protein G/Cellular tumor antigen p53 fusion protein 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: ![]() |
分子量 | 理論値: 43.801734 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MGHHHHHHSS GMTYKLILNG KTLKGETTTE AVDAATAEKV FKQYANDNGV DGEWTYDDAT KTFTVTEEFS SGSSGENLYF QGSHMEEPQ SDPSVEPPLS QETFSDLWKL LPENNVLSPL PSQAMDDLML SPDDIEQWFT EDPGPDEAPR MPEAAPPVAP A PAAPTPAA ...文字列: MGHHHHHHSS GMTYKLILNG KTLKGETTTE AVDAATAEKV FKQYANDNGV DGEWTYDDAT KTFTVTEEFS SGSSGENLYF QGSHMEEPQ SDPSVEPPLS QETFSDLWKL LPENNVLSPL PSQAMDDLML SPDDIEQWFT EDPGPDEAPR MPEAAPPVAP A PAAPTPAA PAPAPSWPLS SSVPSQKTYQ GSYGFRLGFL HSGTAKSVTC TYSPALNKLF CQLAKTCPVQ LWVDSTPPPG TR VRAMAIY KQSQHMTEVV RRCPHHERCS DSDGLAPPQH LIRVEGNLRA EYLDDRNTFR HSVVVPYEPP EVGSDCTTIH YNY MCYSSC MGGMNRRPIL TIITLEDSSG NLLGRDSFEV RVCACPGRDR RTEEENLRKK GEPHHELPPG STKRALPNNT UniProtKB: Immunoglobulin G-binding protein G, Cellular tumor antigen p53 |
-分子 #3: Protein E6
分子 | 名称: Protein E6 / タイプ: protein_or_peptide / ID: 3 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 18.365369 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MFQDPQERPR KLPQLCTELQ TTIHDIILEC VYCKQQLLRR EVYDFAFRDL CIVYRDGNPY AVCDKCLKFY SKISEYRHYC YSLYGTTLE QQYNKPLCDL LIRCINCQKP LCPEEKQRHL DKKQRFHNIR GRWTGRCMSC CRSSRTRRET QL UniProtKB: Protein E6 |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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![]() | 単粒子再構成法 |
試料の集合状態 | particle |
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試料調製
濃度 | 0.25 mg/mL |
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緩衝液 | pH: 7.4 |
グリッド | モデル: Quantifoil R1.2/1.3 |
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 100 % / チャンバー内温度: 279 K |
詳細 | monodisperse, further purified by SEC |
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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: FEI FALCON IV (4k x 4k) 撮影したグリッド数: 1 / 実像数: 5548 / 平均露光時間: 3.192 sec. / 平均電子線量: 1.52 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: ![]() |
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): 1.5 µm / 最小 デフォーカス(公称値): 0.6 µm |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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画像解析
-原子モデル構築 1
初期モデル | Chain - Source name: AlphaFold / Chain - Initial model type: in silico model |
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精密化 | 空間: REAL / プロトコル: RIGID BODY FIT 当てはまり具合の基準: Cross-correlation coefficient |
得られたモデル | ![]() PDB-9cht: |