+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 8oxq | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
タイトル | ATM(Q2971A) dimeric C-terminal region in complex with Mg AMP-PNP | ||||||||||||
要素 | Serine-protein kinase ATM | ||||||||||||
キーワード | SIGNALING PROTEIN / Ataxia-Telangiectasia Mutated / ATM / kinase | ||||||||||||
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 / DNA repair complex / 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 / Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA) / Resolution of D-loop Structures through Holliday Junction Intermediates / HDR through Single Strand Annealing (SSA) / Impaired BRCA2 binding to RAD51 / 1-phosphatidylinositol-3-kinase activity / response to ionizing radiation / mitotic spindle assembly checkpoint signaling / TP53 Regulates Transcription of Caspase Activators and Caspases / negative regulation of B cell proliferation / mitotic G2 DNA damage checkpoint signaling / Presynaptic phase of homologous DNA pairing and strand exchange / peroxisomal matrix / TP53 Regulates Transcription of Genes Involved in Cytochrome C Release / positive regulation of cell adhesion / replicative senescence / Regulation of HSF1-mediated heat shock response / signal transduction in response to DNA damage / somitogenesis / regulation of cellular response to heat / cellular response to retinoic acid / ovarian follicle development / negative regulation of TORC1 signaling / positive regulation of telomere maintenance via telomerase / DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest / Pexophagy / telomere maintenance / post-embryonic development / thymus development / regulation of signal transduction by p53 class mediator / DNA damage checkpoint signaling / regulation of autophagy / determination of adult lifespan / TP53 Regulates Transcription of DNA Repair Genes / Nonhomologous End-Joining (NHEJ) / Stabilization of p53 / Autodegradation of the E3 ubiquitin ligase COP1 / double-strand break repair via homologous recombination / HDR through Homologous Recombination (HRR) / G2/M DNA damage checkpoint / multicellular organism growth / brain development / Regulation of TP53 Activity through Methylation / DNA Damage/Telomere Stress Induced Senescence / cellular response to gamma radiation / Meiotic recombination / cellular response to reactive oxygen species / spindle / double-strand break repair via nonhomologous end joining / intrinsic apoptotic signaling pathway in response to DNA damage / cellular senescence / double-strand break repair / positive regulation of neuron apoptotic process / Regulation of TP53 Degradation / Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks / site of double-strand break / heart development / Processing of DNA double-strand break ends / cytoplasmic vesicle / regulation of apoptotic process / peptidyl-serine phosphorylation / neuron apoptotic process / Regulation of TP53 Activity through Phosphorylation / protein autophosphorylation / non-specific serine/threonine protein kinase / response to hypoxia / regulation of cell cycle / positive regulation of cell migration / positive regulation of apoptotic process / protein phosphorylation 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: 2.5 Å | ||||||||||||
データ登録者 | Howes, A.C. / Perisic, O. / Williams, R.L. | ||||||||||||
資金援助 | 英国, 3件
| ||||||||||||
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 |
|
-構造の表示
構造ビューア | 分子: MolmilJmol/JSmol |
---|
-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 8oxq.cif.gz | 836.6 KB | 表示 | PDBx/mmCIF形式 |
---|---|---|---|---|
PDB形式 | pdb8oxq.ent.gz | 516.5 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 8oxq.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 | 8oxq_validation.pdf.gz | 1.4 MB | 表示 | wwPDB検証レポート |
---|---|---|---|---|
文書・詳細版 | 8oxq_full_validation.pdf.gz | 1.4 MB | 表示 | |
XML形式データ | 8oxq_validation.xml.gz | 90.6 KB | 表示 | |
CIF形式データ | 8oxq_validation.cif.gz | 136.2 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/ox/8oxq ftp://data.pdbj.org/pub/pdb/validation_reports/ox/8oxq | HTTPS FTP |
-関連構造データ
-リンク
-集合体
登録構造単位 |
|
---|---|
1 |
|
-要素
#1: タンパク質 | 分子量: 365005.562 Da / 分子数: 2 / 変異: Q2971A / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: ATM / 発現宿主: Homo sapiens (ヒト) 参照: UniProt: Q13315, non-specific serine/threonine protein kinase #2: 化合物 | #3: 化合物 | #4: 化合物 | 研究の焦点であるリガンドがあるか | Y | |
---|
-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
---|---|
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 bound to Mg AMP-PNP タイプ: COMPLEX 詳細: The map deposited is from local refinement on the C-terminal region of the ATM dimer to obtain higher resolution details. Please note the sample contains the whole ATM dimer itself and not ...詳細: The map deposited is from local refinement on the C-terminal region of the ATM dimer to obtain higher resolution details. Please note the sample contains the whole ATM dimer itself and not just the C-terminal region. Entity ID: #1 / 由来: RECOMBINANT |
---|---|
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 | 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 |
---|---|
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 |
| ||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
EMソフトウェア |
| ||||||||||||||||||||||||||||
CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||
3次元再構成 | 解像度: 2.5 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 1207435 / 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: 142.61 Å2 | ||||||||||||||||||||||||||||
拘束条件 |
|