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Open data
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Basic information
Entry | Database: PDB / ID: 7sud | ||||||
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Title | CryoEM structure of DNA-PK complex VIII | ||||||
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![]() | DNA BINDING PROTEIN / NHEJ / Kinase / DNA repair / DNA-PK | ||||||
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 / regulation of smooth muscle cell proliferation / nuclear telomere cap complex / Cytosolic sensors of pathogen-associated DNA / 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 / double-strand break repair via alternative nonhomologous end joining / telomeric DNA binding / 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 / : / hematopoietic stem cell differentiation / positive regulation of protein kinase activity / ectopic germ cell programmed cell death / ATP-dependent activity, acting on DNA / somitogenesis / DNA helicase activity / enzyme activator activity / mitotic G1 DNA damage checkpoint signaling / positive regulation of telomere maintenance via telomerase / activation of innate immune response / telomere maintenance / neurogenesis / 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 / peptidyl-serine phosphorylation / double-stranded DNA binding / secretory granule lumen / DNA recombination / RNA polymerase II-specific DNA-binding transcription factor binding / 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 / innate immune response / protein serine kinase activity / protein serine/threonine kinase activity / negative regulation of DNA-templated transcription / ubiquitin protein ligase binding / DNA damage response / Neutrophil degranulation Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.6 Å | ||||||
![]() | Chen, X. / Liu, L. / Gellert, M. / Yang, W. | ||||||
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![]() | ![]() Title: Autophosphorylation transforms DNA-PK from protecting to processing DNA ends. Authors: Lan Liu / Xuemin Chen / Jun Li / Huaibin Wang / Christopher J Buehl / Noah J Goff / Katheryn Meek / Wei Yang / Martin Gellert / ![]() Abstract: The DNA-dependent protein kinase (DNA-PK) initially protects broken DNA ends but then promotes their processing during non-homologous end joining (NHEJ). Before ligation by NHEJ, DNA hairpin ends ...The DNA-dependent protein kinase (DNA-PK) initially protects broken DNA ends but then promotes their processing during non-homologous end joining (NHEJ). Before ligation by NHEJ, DNA hairpin ends generated during V(D)J recombination must be opened by the Artemis nuclease, together with autophosphorylated DNA-PK. Structures of DNA-PK bound to DNA before and after phosphorylation, and in complex with Artemis and a DNA hairpin, reveal an essential functional switch. When bound to open DNA ends in its protection mode, DNA-PK is inhibited for cis-autophosphorylation of the so-called ABCDE cluster but activated for phosphorylation of other targets. In contrast, DNA hairpin ends promote cis-autophosphorylation. Phosphorylation of four Thr residues in ABCDE leads to gross structural rearrangement of DNA-PK, widening the DNA binding groove for Artemis recruitment and hairpin cleavage. Meanwhile, Artemis locks DNA-PK into the kinase-inactive state. Kinase activity and autophosphorylation of DNA-PK are regulated by different DNA ends, feeding forward to coordinate NHEJ events. | ||||||
History |
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 682.2 KB | Display | ![]() |
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PDB format | ![]() | 552.7 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 25440MC ![]() 7sglC ![]() 7su3C C: citing same article ( M: map data used to model this data |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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1 |
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Components
#1: Protein | Mass: 469993.031 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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#2: 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 |
#3: Chemical | ChemComp-MG / |
#4: Chemical | ChemComp-ATP / |
Has ligand of interest | Y |
-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: DNA-PK / Type: COMPLEX / Entity ID: #1-#2 / Source: MULTIPLE SOURCES |
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Buffer solution | pH: 7.9 |
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 |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
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Processing
Software | Name: PHENIX / Version: 1.14_3260: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.6 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 42521 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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