+Open data
-Basic information
Entry | Database: PDB / ID: 8oxq | ||||||||||||
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Title | ATM(Q2971A) dimeric C-terminal region in complex with Mg AMP-PNP | ||||||||||||
Components | Serine-protein kinase ATM | ||||||||||||
Keywords | SIGNALING PROTEIN / Ataxia-Telangiectasia Mutated / ATM / kinase | ||||||||||||
Function / homology | Function and homology information 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 / pre-B cell allelic exclusion / DNA-dependent protein kinase activity / histone H2AXS139 kinase activity / male meiotic nuclear division / histone mRNA catabolic process / 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 / TP53 Regulates Transcription of Genes Involved in Cytochrome C Release / peroxisomal matrix / 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 / multicellular organism growth / HDR through Homologous Recombination (HRR) / G2/M DNA damage checkpoint / 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 / double-strand break repair via nonhomologous end joining / spindle / intrinsic apoptotic signaling pathway in response to DNA damage / positive regulation of neuron apoptotic process / cellular senescence / double-strand break repair / Regulation of TP53 Degradation / Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks / heart development / site of double-strand break / Processing of DNA double-strand break ends / cytoplasmic vesicle / peptidyl-serine phosphorylation / regulation of apoptotic process / neuron apoptotic process / Regulation of TP53 Activity through Phosphorylation / protein autophosphorylation / response to hypoxia / regulation of cell cycle / non-specific serine/threonine protein kinase / positive regulation of cell migration / positive regulation of apoptotic process / protein phosphorylation Similarity search - Function | ||||||||||||
Biological species | Homo sapiens (human) | ||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.5 Å | ||||||||||||
Authors | Howes, A.C. / Perisic, O. / Williams, R.L. | ||||||||||||
Funding support | United Kingdom, 3items
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Citation | Journal: Sci Adv / Year: 2023 Title: Structural insights into the activation of ataxia-telangiectasia mutated by oxidative stress. Authors: Anna C Howes / Olga Perisic / Roger L Williams / Abstract: 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. | ||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8oxq.cif.gz | 836.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8oxq.ent.gz | 516.5 KB | Display | PDB format |
PDBx/mmJSON format | 8oxq.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8oxq_validation.pdf.gz | 1.4 MB | Display | wwPDB validaton report |
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Full document | 8oxq_full_validation.pdf.gz | 1.4 MB | Display | |
Data in XML | 8oxq_validation.xml.gz | 90.6 KB | Display | |
Data in CIF | 8oxq_validation.cif.gz | 136.2 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ox/8oxq ftp://data.pdbj.org/pub/pdb/validation_reports/ox/8oxq | HTTPS FTP |
-Related structure data
Related structure data | 17268MC 8oxmC 8oxoC 8oxpC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 365005.562 Da / Num. of mol.: 2 / Mutation: Q2971A Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ATM / Production host: Homo sapiens (human) References: UniProt: Q13315, non-specific serine/threonine protein kinase #2: Chemical | #3: Chemical | #4: Chemical | Has ligand of interest | Y | |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: ATM(Q2971A) dimeric C-terminal region bound to Mg AMP-PNP Type: COMPLEX Details: 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 ...Details: 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 / Source: RECOMBINANT |
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Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Homo sapiens (human) / Cell: Kidney (Embryonic) |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 105000 X / Nominal defocus max: 3000 nm / Nominal defocus min: 1000 nm |
Specimen holder | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 39.5 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
Software |
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||
3D reconstruction | Resolution: 2.5 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 1207435 / Symmetry type: POINT | ||||||||||||||||||||||||||||
Atomic model building | PDB-ID: 7SIC Accession code: 7SIC / Source name: PDB / Type: experimental model | ||||||||||||||||||||||||||||
Refinement | Cross valid method: NONE Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 142.61 Å2 | ||||||||||||||||||||||||||||
Refine LS restraints |
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