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Open data
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Basic information
Entry | Database: PDB / ID: 7z88 | ||||||
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Title | DNA-PK in the intermediate state | ||||||
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![]() | DNA BINDING PROTEIN / DNA-dependent protein kinase | ||||||
Function / homology | ![]() Ku70:Ku80 complex / negative regulation of t-circle formation / positive regulation of platelet formation / DNA end binding / T cell receptor V(D)J recombination / pro-B cell differentiation / small-subunit processome assembly / positive regulation of lymphocyte differentiation / DNA-dependent protein kinase activity / histone H2AXS139 kinase activity ...Ku70:Ku80 complex / negative regulation of t-circle formation / positive regulation of platelet formation / DNA end binding / T cell receptor V(D)J recombination / pro-B cell differentiation / small-subunit processome assembly / positive regulation of lymphocyte differentiation / DNA-dependent protein kinase activity / histone H2AXS139 kinase activity / DNA-dependent protein kinase complex / immature B cell differentiation / DNA-dependent protein kinase-DNA ligase 4 complex / cellular response to X-ray / immunoglobulin V(D)J recombination / nonhomologous end joining complex / DNA ligation / regulation of smooth muscle cell proliferation / nuclear telomere cap complex / Cytosolic sensors of pathogen-associated DNA / double-strand break repair via classical nonhomologous end joining / regulation of epithelial cell proliferation / IRF3-mediated induction of type I IFN / telomere capping / recombinational repair / regulation of hematopoietic stem cell differentiation / regulation of telomere maintenance / U3 snoRNA binding / protein localization to chromosome, telomeric region / cellular response to fatty acid / positive regulation of neurogenesis / hematopoietic stem cell proliferation / cellular hyperosmotic salinity response / positive regulation of catalytic activity / T cell lineage commitment / negative regulation of cGAS/STING signaling pathway / telomeric DNA binding / double-strand break repair via alternative nonhomologous end joining / maturation of 5.8S rRNA / B cell lineage commitment / 2-LTR circle formation / positive regulation of double-strand break repair via nonhomologous end joining / : / site of DNA damage / Lyases; Carbon-oxygen lyases; Other carbon-oxygen lyases / 5'-deoxyribose-5-phosphate lyase activity / hematopoietic stem cell differentiation / positive regulation of protein kinase activity / ectopic germ cell programmed cell death / ATP-dependent activity, acting on DNA / somitogenesis / enzyme activator activity / mitotic G1 DNA damage checkpoint signaling / positive regulation of telomere maintenance via telomerase / activation of innate immune response / DNA helicase activity / telomere maintenance / neurogenesis / cyclin binding / positive regulation of erythrocyte differentiation / negative regulation of protein phosphorylation / cellular response to leukemia inhibitory factor / small-subunit processome / positive regulation of translation / protein-DNA complex / response to gamma radiation / Nonhomologous End-Joining (NHEJ) / peptidyl-threonine phosphorylation / Hydrolases; Acting on acid anhydrides; Acting on acid anhydrides to facilitate cellular and subcellular movement / protein destabilization / protein modification process / brain development / regulation of circadian rhythm / cellular response to gamma radiation / double-strand break repair via nonhomologous end joining / cellular response to insulin stimulus / intrinsic apoptotic signaling pathway in response to DNA damage / double-strand break repair / rhythmic process / E3 ubiquitin ligases ubiquitinate target proteins / heart development / T cell differentiation in thymus / scaffold protein binding / double-stranded DNA binding / peptidyl-serine phosphorylation / secretory granule lumen / DNA recombination / RNA polymerase II-specific DNA-binding transcription factor binding / ficolin-1-rich granule lumen / transcription regulator complex / damaged DNA binding / chromosome, telomeric region / non-specific serine/threonine protein kinase / transcription cis-regulatory region binding / protein kinase activity / ribonucleoprotein complex / response to xenobiotic stimulus / positive regulation of apoptotic process / protein domain specific binding / protein phosphorylation Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.33 Å | ||||||
![]() | Liang, S. / Blundell, T.L. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Human DNA-dependent protein kinase activation mechanism. Authors: Shikang Liang / Tom L Blundell / ![]() Abstract: DNA-dependent protein kinase (DNA-PK), a multicomponent complex including the DNA-PK catalytic subunit and Ku70/80 heterodimer together with DNA, is central to human DNA damage response and repair. ...DNA-dependent protein kinase (DNA-PK), a multicomponent complex including the DNA-PK catalytic subunit and Ku70/80 heterodimer together with DNA, is central to human DNA damage response and repair. Using a DNA-PK-selective inhibitor (M3814), we identified from one dataset two cryo-EM structures of the human DNA-PK complex in different states, the intermediate state and the active state. Here we show that activation of the kinase is regulated through conformational changes caused by the binding ligand and the string region (residues 802-846) of the DNA-PK catalytic subunit, particularly the helix-hairpin-helix motif (residues 816-836) that interacts with DNA. These observations demonstrate the regulatory role of the ligand and explain why DNA-PK is DNA dependent. Cooperation and coordination among binding partners, disordered flexible regions and mechanically flexible HEAT repeats modulate the activation of the kinase. Together with previous findings, these results provide a better molecular understanding of DNA-PK catalysis. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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PDBx/mmCIF format | ![]() | 873.1 KB | Display | ![]() |
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PDB format | ![]() | 694.3 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 14546MC ![]() 7z87C M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
-X-ray repair cross-complementing protein ... , 2 types, 2 molecules BC
#2: Protein | Mass: 69945.039 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() References: UniProt: P12956, Hydrolases; Acting on acid anhydrides; Acting on acid anhydrides to facilitate cellular and subcellular movement, Lyases; Carbon-oxygen lyases; Other carbon-oxygen lyases |
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#3: Protein | Mass: 82812.438 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() References: UniProt: P13010, Hydrolases; Acting on acid anhydrides; Acting on acid anhydrides to facilitate cellular and subcellular movement |
-DNA chain , 2 types, 2 molecules DE
#4: DNA chain | Mass: 7900.079 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) ![]() |
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#5: DNA chain | Mass: 8078.203 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) ![]() |
-Protein / Non-polymers , 2 types, 2 molecules A![](data/chem/img/1IX.gif)
![](data/chem/img/1IX.gif)
#1: Protein | Mass: 469673.219 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() References: UniProt: P78527, non-specific serine/threonine protein kinase |
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#6: Chemical | ChemComp-1IX / (~{ |
-Details
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 |
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Sample preparation
Component | Name: Human DNA-dependent protein kinase / Type: COMPLEX / Entity ID: #1-#5 / Source: NATURAL |
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Source (natural) | Organism: ![]() |
Buffer solution | pH: 7.6 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
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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: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2300 nm / Nominal defocus min: 1100 nm |
Image recording | Electron dose: 47.22 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
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Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3D reconstruction | Resolution: 3.33 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 190498 / Symmetry type: POINT |