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Open data
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Basic information
| Entry | Database: PDB / ID: 8rd4 | |||||||||||||||
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| Title | Telomeric RAP1:DNA-PK complex | |||||||||||||||
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Keywords | DNA BINDING PROTEIN / Telomere NHEJ BRCT domain SAP domain | |||||||||||||||
| Function / homology | Function and homology informationnegative regulation of DNA recombination at telomere / protection from non-homologous end joining at telomere / positive regulation of platelet formation / Ku70:Ku80 complex / negative regulation of telomere maintenance / negative regulation of t-circle formation / T cell receptor V(D)J recombination / DNA end binding / pro-B cell differentiation / shelterin complex ...negative regulation of DNA recombination at telomere / protection from non-homologous end joining at telomere / positive regulation of platelet formation / Ku70:Ku80 complex / negative regulation of telomere maintenance / negative regulation of t-circle formation / T cell receptor V(D)J recombination / DNA end binding / pro-B cell differentiation / shelterin complex / small-subunit processome assembly / positive regulation of lymphocyte differentiation / telomere maintenance via telomere lengthening / DNA-dependent protein kinase activity / Telomere C-strand synthesis initiation / DNA-dependent protein kinase complex / histone H2AXS139 kinase activity / DNA-dependent protein kinase-DNA ligase 4 complex / immunoglobulin V(D)J recombination / nonhomologous end joining complex / immature B cell differentiation / regulation of smooth muscle cell proliferation / cellular response to X-ray / Telomere C-strand (Lagging Strand) Synthesis / nuclear telomere cap complex / double-strand break repair via alternative nonhomologous end joining / G-rich strand telomeric DNA binding / regulation of epithelial cell proliferation / double-strand break repair via classical nonhomologous end joining / telomere capping / Cytosolic sensors of pathogen-associated DNA / Processive synthesis on the C-strand of the telomere / Polymerase switching on the C-strand of the telomere / IRF3-mediated induction of type I IFN / Removal of the Flap Intermediate from the C-strand / regulation of hematopoietic stem cell differentiation / positive regulation of neurogenesis / recombinational repair / regulation of telomere maintenance / protein localization to chromosome, telomeric region / U3 snoRNA binding / maturation of 5.8S rRNA / T cell lineage commitment / cellular hyperosmotic salinity response / regulation of double-strand break repair via homologous recombination / negative regulation of cGAS/STING signaling pathway / positive regulation of double-strand break repair via nonhomologous end joining / nuclear chromosome / 2-LTR circle formation / B cell lineage commitment / telomeric DNA binding / hematopoietic stem cell proliferation / negative regulation of protein phosphorylation / positive regulation of telomere maintenance / positive regulation of protein kinase activity / Lyases; Carbon-oxygen lyases; Other carbon-oxygen lyases / site of DNA damage / peptidyl-threonine phosphorylation / Telomere Extension By Telomerase / 5'-deoxyribose-5-phosphate lyase activity / hematopoietic stem cell differentiation / ectopic germ cell programmed cell death / ATP-dependent activity, acting on DNA / telomere maintenance via telomerase / somitogenesis / phosphatase binding / Packaging Of Telomere Ends / mitotic G1 DNA damage checkpoint signaling / neurogenesis / Recognition and association of DNA glycosylase with site containing an affected purine / Cleavage of the damaged purine / Recognition and association of DNA glycosylase with site containing an affected pyrimidine / Cleavage of the damaged pyrimidine / telomere maintenance / activation of innate immune response / DNA helicase activity / Inhibition of DNA recombination at telomere / cyclin binding / Meiotic synapsis / positive regulation of erythrocyte differentiation / positive regulation of translation / cellular response to leukemia inhibitory factor / response to gamma radiation / male germ cell nucleus / small-subunit processome / Nonhomologous End-Joining (NHEJ) / enzyme activator activity / positive regulation of non-canonical NF-kappaB signal transduction / cellular response to gamma radiation / positive regulation of NF-kappaB transcription factor activity / protein-DNA complex / regulation of circadian rhythm / brain development / peptidyl-serine phosphorylation / protein destabilization / protein modification process / double-strand break repair via nonhomologous end joining / DNA Damage/Telomere Stress Induced Senescence / Hydrolases; Acting on acid anhydrides; Acting on acid anhydrides to facilitate cellular and subcellular movement / cellular response to insulin stimulus Similarity search - Function | |||||||||||||||
| Biological species | Homo sapiens (human)synthetic construct (others) | |||||||||||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.58 Å | |||||||||||||||
Authors | Eickhoff, P. / Fisher, C.E.L. / Inian, O. / Guettler, S. / Douglas, M.E. | |||||||||||||||
| Funding support | United Kingdom, 1items
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Citation | Journal: Nature / Year: 2025Title: Chromosome end protection by RAP1-mediated inhibition of DNA-PK. Authors: Patrik Eickhoff / Ceylan Sonmez / Charlotte E L Fisher / Oviya Inian / Theodoros I Roumeliotis / Angela Dello Stritto / Jörg Mansfeld / Jyoti S Choudhary / Sebastian Guettler / Francisca ...Authors: Patrik Eickhoff / Ceylan Sonmez / Charlotte E L Fisher / Oviya Inian / Theodoros I Roumeliotis / Angela Dello Stritto / Jörg Mansfeld / Jyoti S Choudhary / Sebastian Guettler / Francisca Lottersberger / Max E Douglas / ![]() Abstract: During classical non-homologous end joining (cNHEJ), DNA-dependent protein kinase (DNA-PK) encapsulates free DNA ends, forming a recruitment platform for downstream end-joining factors including ...During classical non-homologous end joining (cNHEJ), DNA-dependent protein kinase (DNA-PK) encapsulates free DNA ends, forming a recruitment platform for downstream end-joining factors including ligase 4 (LIG4). DNA-PK can also bind telomeres and regulate their resection, but does not initiate cNHEJ at this position. How the end-joining process is regulated in this context-specific manner is currently unclear. Here we show that the shelterin components TRF2 and RAP1 form a complex with DNA-PK that directly represses its end-joining function at telomeres. Biochemical experiments and cryo-electron microscopy reveal that when bound to TRF2, RAP1 establishes a network of interactions with KU and DNA that prevents DNA-PK from recruiting LIG4. In mouse and human cells, RAP1 is redundant with the Apollo nuclease in repressing cNHEJ at chromosome ends, demonstrating that the inhibition of DNA-PK prevents telomere fusions in parallel with overhang-dependent mechanisms. Our experiments show that the end-joining function of DNA-PK is directly and specifically repressed at telomeres, establishing a molecular mechanism for how individual linear chromosomes are maintained in mammalian cells. | |||||||||||||||
| History |
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Structure visualization
| Structure viewer | Molecule: Molmil Jmol/JSmol |
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Downloads & links
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Download
| PDBx/mmCIF format | 8rd4.cif.gz | 921.9 KB | Display | PDBx/mmCIF format |
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| PDB format | pdb8rd4.ent.gz | 732.5 KB | Display | PDB format |
| PDBx/mmJSON format | 8rd4.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Summary document | 8rd4_validation.pdf.gz | 935.7 KB | Display | wwPDB validaton report |
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| Full document | 8rd4_full_validation.pdf.gz | 1022.5 KB | Display | |
| Data in XML | 8rd4_validation.xml.gz | 128.8 KB | Display | |
| Data in CIF | 8rd4_validation.cif.gz | 195.3 KB | Display | |
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/rd/8rd4 ftp://data.pdbj.org/pub/pdb/validation_reports/rd/8rd4 | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 19065MC M: map data used to model this data C: citing same article ( |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
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Assembly
| Deposited unit | ![]()
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Components
-Protein , 2 types, 2 molecules AD
| #1: Protein | Mass: 469673.219 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human)References: UniProt: P78527, non-specific serine/threonine protein kinase |
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| #2: Protein | Mass: 44314.871 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: TERF2IP / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: Q9NYB0 |
-X-ray repair cross-complementing protein ... , 2 types, 2 molecules EF
| #3: Protein | Mass: 69945.039 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: XRCC6, G22P1 / Production host: Trichoplusia ni (cabbage looper)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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| #4: Protein | Mass: 82812.438 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: XRCC5, G22P2 / Production host: Trichoplusia ni (cabbage looper)References: UniProt: P13010, Hydrolases; Acting on acid anhydrides; Acting on acid anhydrides to facilitate cellular and subcellular movement |
-DNA chain , 2 types, 2 molecules XY
| #5: DNA chain | Mass: 31103.840 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others) |
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| #6: DNA chain | Mass: 30589.674 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others) |
-Details
| Has protein modification | N |
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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: Telomeric RAP1:DNA-PK complex / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
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| Source (natural) | Organism: Homo sapiens (human) |
| Source (recombinant) | Organism: Trichoplusia ni (cabbage looper) |
| 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
| Microscopy | Model: TFS GLACIOS |
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| Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: FLOOD BEAM |
| Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2500 nm / Nominal defocus min: 1000 nm |
| Image recording | Electron dose: 50 e/Å2 / Film or detector model: TFS FALCON 4i (4k x 4k) |
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Processing
| CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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| 3D reconstruction | Resolution: 3.58 Å / Resolution method: OTHER / Num. of particles: 526885 Details: Composite map, resolution estimated from overall consensus map using a FSC 0.143 cut-off Symmetry type: POINT |
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About Yorodumi




Homo sapiens (human)
United Kingdom, 1items
Citation




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Trichoplusia ni (cabbage looper)
FIELD EMISSION GUN