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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-11219 | |||||||||
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Title | Cryo-EM structure of DNA-PK dimer | |||||||||
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Function / homology | ![]() Ku70:Ku80 complex / negative regulation of t-circle formation / positive regulation of platelet formation / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | ![]() ![]() | |||||||||
![]() | Chaplin AK / Hardwick SW | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Dimers of DNA-PK create a stage for DNA double-strand break repair. Authors: Amanda K Chaplin / Steven W Hardwick / Shikang Liang / Antonia Kefala Stavridi / Ales Hnizda / Lee R Cooper / Taiana Maia De Oliveira / Dimitri Y Chirgadze / Tom L Blundell / ![]() Abstract: DNA double-strand breaks are the most dangerous type of DNA damage and, if not repaired correctly, can lead to cancer. In humans, Ku70/80 recognizes DNA broken ends and recruits the DNA-dependent ...DNA double-strand breaks are the most dangerous type of DNA damage and, if not repaired correctly, can lead to cancer. In humans, Ku70/80 recognizes DNA broken ends and recruits the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) to form DNA-dependent protein kinase holoenzyme (DNA-PK) in the process of non-homologous end joining (NHEJ). We present a 2.8-Å-resolution cryo-EM structure of DNA-PKcs, allowing precise amino acid sequence registration in regions uninterpreted in previous 4.3-Å X-ray maps. We also report a cryo-EM structure of DNA-PK at 3.5-Å resolution and reveal a dimer mediated by the Ku80 C terminus. Central to dimer formation is a domain swap of the conserved C-terminal helix of Ku80. Our results suggest a new mechanism for NHEJ utilizing a DNA-PK dimer to bring broken DNA ends together. Furthermore, drug inhibition of NHEJ in combination with chemo- and radiotherapy has proved successful, making these models central to structure-based drug targeting efforts. #1: ![]() Title: Dimers of DNA-PK create a stage for DNA-double strand break repair Authors: Chaplin AK / Hardwick SW / Liang S / Stavridi AK / Hnizda A / Cooper LR / De Oliveira TM / Chirgadze DY / Blundell TL | |||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 631.9 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 29.8 KB 29.8 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 25.9 KB | Display | ![]() |
Images | ![]() | 32.9 KB | ||
Filedesc metadata | ![]() | 9.9 KB | ||
Others | ![]() ![]() ![]() | 64.1 MB 622.3 MB 622.3 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6zheMC ![]() 6zfpC ![]() 6zh2C ![]() 6zh4C ![]() 6zh6C ![]() 6zh8C ![]() 6zhaC M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Voxel size | X=Y=Z: 1.05 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Additional map: Resolve cryoEM density modified map at 5.72 angstrom resolution
File | emd_11219_additional_1.map | ||||||||||||
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Annotation | Resolve cryoEM density modified map at 5.72 angstrom resolution | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_11219_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_11219_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
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Sample components
+Entire : DNA-PK dimer
+Supramolecule #1: DNA-PK dimer
+Supramolecule #2: DNA-dependent protein kinase catalytic subunit
+Supramolecule #3: X-ray repair cross-complementing proteins 5 and 6
+Supramolecule #4: DNA
+Macromolecule #1: DNA-dependent protein kinase catalytic subunit,DNA-PKcs
+Macromolecule #2: X-ray repair cross-complementing protein 6
+Macromolecule #3: X-ray repair cross-complementing protein 5
+Macromolecule #4: DNA (25-MER)
+Macromolecule #5: DNA (27-MER)
+Macromolecule #6: DNA (26-MER)
+Macromolecule #7: DNA (28-MER)
-Experimental details
-Structure determination
Method | ![]() |
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Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD![]() |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Average electron dose: 52.97 e/Å2 |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |