+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 8oxo | ||||||||||||
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タイトル | ATM(Q2971A) dimeric C-terminal region activated by oxidative stress in complex with Mg AMP-PNP and p53 peptide | ||||||||||||
要素 |
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キーワード | SIGNALING PROTEIN / Kinase / Ataxia-Telangiectasia Mutated / ATM / p53 | ||||||||||||
機能・相同性 | 機能・相同性情報 positive regulation of DNA catabolic process / establishment of RNA localization to telomere / positive regulation of telomerase catalytic core complex assembly / positive regulation of DNA damage response, signal transduction by p53 class mediator / cellular response to nitrosative stress / establishment of protein-containing complex localization to telomere / regulation of microglial cell activation / negative regulation of telomere capping / Sensing of DNA Double Strand Breaks / positive regulation of telomere maintenance via telomere lengthening ...positive regulation of DNA catabolic process / establishment of RNA localization to telomere / positive regulation of telomerase catalytic core complex assembly / positive regulation of DNA damage response, signal transduction by p53 class mediator / cellular response to nitrosative stress / establishment of protein-containing complex localization to telomere / regulation of microglial cell activation / negative regulation of telomere capping / Sensing of DNA Double Strand Breaks / positive regulation of telomere maintenance via telomere lengthening / meiotic telomere clustering / DNA-dependent protein kinase activity / histone H2AXS139 kinase activity / male meiotic nuclear division / histone mRNA catabolic process / pre-B cell allelic exclusion / female meiotic nuclear division / pexophagy / cellular response to X-ray / regulation of telomere maintenance via telomerase / peptidyl-serine autophosphorylation / lipoprotein catabolic process / V(D)J recombination / oocyte development / Impaired BRCA2 binding to PALB2 / reciprocal meiotic recombination / 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 / Activation of NOXA and translocation to mitochondria / negative regulation of pentose-phosphate shunt / ATP-dependent DNA/DNA annealing activity / negative regulation of helicase activity / regulation of cell cycle G2/M phase transition / intrinsic apoptotic signaling pathway in response to hypoxia / regulation of fibroblast apoptotic process / DNA repair complex / oxidative stress-induced premature senescence / oligodendrocyte apoptotic process / negative regulation of miRNA processing / positive regulation of thymocyte apoptotic process / glucose catabolic process to lactate via pyruvate / regulation of tissue remodeling / positive regulation of mitochondrial membrane permeability / negative regulation of mitophagy / positive regulation of programmed necrotic cell death / Defective homologous recombination repair (HRR) due to BRCA1 loss of function / Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function / Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function / Homologous DNA Pairing and Strand Exchange / mRNA transcription / bone marrow development / Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA) / circadian behavior / histone deacetylase regulator activity / RUNX3 regulates CDKN1A transcription / germ cell nucleus / regulation of mitochondrial membrane permeability involved in apoptotic process / regulation of DNA damage response, signal transduction by p53 class mediator / Resolution of D-loop Structures through Holliday Junction Intermediates / TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain / TP53 Regulates Transcription of Death Receptors and Ligands / Activation of PUMA and translocation to mitochondria / DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator / HDR through Single Strand Annealing (SSA) / negative regulation of glial cell proliferation / Formation of Senescence-Associated Heterochromatin Foci (SAHF) / negative regulation of neuroblast proliferation / Impaired BRCA2 binding to RAD51 / Regulation of TP53 Activity through Association with Co-factors / 1-phosphatidylinositol-3-kinase activity / mitochondrial DNA repair / response to ionizing radiation / T cell lineage commitment / negative regulation of DNA replication / ER overload response / mitotic spindle assembly checkpoint signaling / B cell lineage commitment / positive regulation of cardiac muscle cell apoptotic process / thymocyte apoptotic process / TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain / TP53 Regulates Transcription of Caspase Activators and Caspases / cardiac septum morphogenesis / negative regulation of B cell proliferation / positive regulation of execution phase of apoptosis / entrainment of circadian clock by photoperiod / PI5P Regulates TP53 Acetylation / Association of TriC/CCT with target proteins during biosynthesis / mitotic G2 DNA damage checkpoint signaling / Zygotic genome activation (ZGA) / necroptotic process / positive regulation of release of cytochrome c from mitochondria / Presynaptic phase of homologous DNA pairing and strand exchange / peroxisomal matrix / TP53 Regulates Transcription of Genes Involved in Cytochrome C Release / rRNA transcription 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: 3 Å | ||||||||||||
データ登録者 | Howes, A.C. / Perisic, O. / Williams, R.L. | ||||||||||||
資金援助 | 英国, 3件
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引用 | ジャーナル: Sci Adv / 年: 2023 タイトル: Structural insights into the activation of ataxia-telangiectasia mutated by oxidative stress. 著者: Anna C Howes / Olga Perisic / Roger L Williams / 要旨: Ataxia-telangiectasia mutated (ATM) is a master kinase regulating DNA damage response that is activated by DNA double-strand breaks. However, ATM is also directly activated by reactive oxygen ...Ataxia-telangiectasia mutated (ATM) is a master kinase regulating DNA damage response that is activated by DNA double-strand breaks. However, ATM is also directly activated by reactive oxygen species, but how oxidative activation is achieved remains unknown. We determined the cryo-EM structure of an HO-activated ATM and showed that under oxidizing conditions, ATM formed an intramolecular disulfide bridge between two protomers that are rotated relative to each other when compared to the basal state. This rotation is accompanied by release of the substrate-blocking PRD region and twisting of the N-lobe relative to the C-lobe, which greatly optimizes catalysis. This active site remodeling enabled us to capture a substrate (p53) bound to the enzyme. This provides the first structural insights into how ATM is activated during oxidative stress. | ||||||||||||
履歴 |
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-構造の表示
構造ビューア | 分子: MolmilJmol/JSmol |
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-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 8oxo.cif.gz | 809.1 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb8oxo.ent.gz | 497.3 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 8oxo.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
文書・要旨 | 8oxo_validation.pdf.gz | 1.8 MB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 8oxo_full_validation.pdf.gz | 1.8 MB | 表示 | |
XML形式データ | 8oxo_validation.xml.gz | 90.9 KB | 表示 | |
CIF形式データ | 8oxo_validation.cif.gz | 135.8 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/ox/8oxo ftp://data.pdbj.org/pub/pdb/validation_reports/ox/8oxo | HTTPS FTP |
-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
#1: タンパク質・ペプチド | 分子量: 1362.438 Da / 分子数: 2 / 由来タイプ: 合成 / 詳細: Custom synthesized peptide / 由来: (合成) Homo sapiens (ヒト) / 参照: UniProt: P04637 #2: タンパク質 | 分子量: 365005.562 Da / 分子数: 2 / Mutation: Q2971A / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: ATM / Cell (発現宿主): Kidney (Embryonic) / 細胞株 (発現宿主): Expi293F / 発現宿主: Homo sapiens (ヒト) 参照: UniProt: Q13315, non-specific serine/threonine protein kinase #3: 化合物 | #4: 化合物 | #5: 化合物 | 研究の焦点であるリガンドがあるか | Y | |
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-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: ATM(Q2971A) dimeric C-terminal region activated by H2O2 and bound to Mg AMP-PNP and p53 substrate peptide タイプ: COMPLEX 詳細: Only the C-terminal region of the ATM (Q2971A) dimer from local refinement is shown, with AMP-PNP and p53 substrate peptide bound in the structure. Please note, the whole dimer molecule is present in the sample. Entity ID: #1-#2 / 由来: RECOMBINANT |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
由来(組換発現) | 生物種: Homo sapiens (ヒト) / 細胞: Kidney (Embryonic) |
緩衝液 | pH: 7.5 |
試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
急速凍結 | 装置: FEI VITROBOT MARK IV / 凍結剤: ETHANE |
-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 FIELD / 倍率(公称値): 105000 X / 最大 デフォーカス(公称値): 3000 nm / 最小 デフォーカス(公称値): 1000 nm |
試料ホルダ | 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER |
撮影 | 電子線照射量: 39.5 e/Å2 / フィルム・検出器のモデル: GATAN K3 (6k x 4k) |
-解析
ソフトウェア |
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EMソフトウェア |
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||
対称性 | 点対称性: C2 (2回回転対称) | ||||||||||||||||||||||||||||
3次元再構成 | 解像度: 3 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 30707 / 対称性のタイプ: POINT | ||||||||||||||||||||||||||||
原子モデル構築 | PDB-ID: 7SIC Accession code: 7SIC / Source name: PDB / タイプ: experimental model | ||||||||||||||||||||||||||||
精密化 | 交差検証法: NONE 立体化学のターゲット値: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||||||
原子変位パラメータ | Biso mean: 152.88 Å2 | ||||||||||||||||||||||||||||
拘束条件 |
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