+Open data
-Basic information
Entry | Database: PDB / ID: 8ox1 | ||||||||||||
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Title | Structure of TRF1core in complex with telomeric nucleosome | ||||||||||||
Components |
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Keywords | DNA BINDING PROTEIN / Telomeric nucleosome / shelterin / telomere | ||||||||||||
Function / homology | Function and homology information positive regulation of shelterin complex assembly / negative regulation of establishment of protein localization to telomere / negative regulation of establishment of RNA localization to telomere / negative regulation of establishment of protein-containing complex localization to telomere / negative regulation of telomere maintenance via semi-conservative replication / negative regulation of exonuclease activity / negative regulation of telomeric D-loop disassembly / meiotic telomere clustering / telomerase activity / t-circle formation ...positive regulation of shelterin complex assembly / negative regulation of establishment of protein localization to telomere / negative regulation of establishment of RNA localization to telomere / negative regulation of establishment of protein-containing complex localization to telomere / negative regulation of telomere maintenance via semi-conservative replication / negative regulation of exonuclease activity / negative regulation of telomeric D-loop disassembly / meiotic telomere clustering / telomerase activity / t-circle formation / telomeric D-loop disassembly / shelterin complex / Telomere C-strand synthesis initiation / double-stranded telomeric DNA binding / Telomere C-strand (Lagging Strand) Synthesis / negative regulation of telomerase activity / positive regulation of telomere maintenance / nuclear telomere cap complex / ankyrin repeat binding / Processive synthesis on the C-strand of the telomere / Polymerase switching on the C-strand of the telomere / Removal of the Flap Intermediate from the C-strand / G-rich strand telomeric DNA binding / telomere capping / DNA binding, bending / negative regulation of telomere maintenance via telomere lengthening / telomeric DNA binding / negative regulation of DNA replication / negative regulation of telomere maintenance via telomerase / Telomere Extension By Telomerase / telomere maintenance via telomerase / negative regulation of megakaryocyte differentiation / protein localization to CENP-A containing chromatin / Chromatin modifying enzymes / Replacement of protamines by nucleosomes in the male pronucleus / CENP-A containing nucleosome / heterochromatin organization / epigenetic regulation of gene expression / Packaging Of Telomere Ends / Recognition and association of DNA glycosylase with site containing an affected purine / Cleavage of the damaged purine / Deposition of new CENPA-containing nucleosomes at the centromere / nucleosomal DNA binding / Recognition and association of DNA glycosylase with site containing an affected pyrimidine / Cleavage of the damaged pyrimidine / Inhibition of DNA recombination at telomere / Meiotic synapsis / telomere organization / RNA Polymerase I Promoter Opening / Interleukin-7 signaling / telomere maintenance / Assembly of the ORC complex at the origin of replication / SUMOylation of chromatin organization proteins / DNA methylation / Condensation of Prophase Chromosomes / ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression / SIRT1 negatively regulates rRNA expression / Chromatin modifications during the maternal to zygotic transition (MZT) / HCMV Late Events / innate immune response in mucosa / PRC2 methylates histones and DNA / Defective pyroptosis / HDACs deacetylate histones / RNA Polymerase I Promoter Escape / Nonhomologous End-Joining (NHEJ) / Transcriptional regulation by small RNAs / Formation of the beta-catenin:TCF transactivating complex / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / NoRC negatively regulates rRNA expression / Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3 / B-WICH complex positively regulates rRNA expression / G2/M DNA damage checkpoint / HDMs demethylate histones / DNA Damage/Telomere Stress Induced Senescence / Metalloprotease DUBs / PKMTs methylate histone lysines / fibrillar center / Meiotic recombination / RMTs methylate histone arginines / Pre-NOTCH Transcription and Translation / Activation of anterior HOX genes in hindbrain development during early embryogenesis / HCMV Early Events / spindle / Transcriptional regulation of granulopoiesis / structural constituent of chromatin / antimicrobial humoral immune response mediated by antimicrobial peptide / UCH proteinases / nucleosome / nucleosome assembly / E3 ubiquitin ligases ubiquitinate target proteins / Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks / chromatin organization / RUNX1 regulates transcription of genes involved in differentiation of HSCs / Factors involved in megakaryocyte development and platelet production / gene expression / HATs acetylate histones / Processing of DNA double-strand break ends / antibacterial humoral response / Senescence-Associated Secretory Phenotype (SASP) / microtubule binding Similarity search - Function | ||||||||||||
Biological species | Homo sapiens (human) | ||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.7 Å | ||||||||||||
Authors | Hu, H. / van Roon, A.M.M. / Ghanim, G.E. / Ahsan, B. / Oluwole, A. / Peak-Chew, S. / Robinson, C.V. / Nguyen, T.H.D. | ||||||||||||
Funding support | United Kingdom, European Union, United States, 3items
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Citation | Journal: Sci Adv / Year: 2023 Title: Structural basis of telomeric nucleosome recognition by shelterin factor TRF1. Authors: Hongmiao Hu / Anne-Marie M van Roon / George E Ghanim / Bilal Ahsan / Abraham O Oluwole / Sew-Yeu Peak-Chew / Carol V Robinson / Thi Hoang Duong Nguyen / Abstract: Shelterin and nucleosomes are the key players that organize mammalian chromosome ends into the protective telomere caps. However, how they interact with each other at telomeres remains unknown. We ...Shelterin and nucleosomes are the key players that organize mammalian chromosome ends into the protective telomere caps. However, how they interact with each other at telomeres remains unknown. We report cryo-electron microscopy structures of a human telomeric nucleosome both unbound and bound to the shelterin factor TRF1. Our structures reveal that TRF1 binds unwrapped nucleosomal DNA ends by engaging both the nucleosomal DNA and the histone octamer. Unexpectedly, TRF1 binding shifts the register of the nucleosomal DNA by 1 bp. We discovered that phosphorylation of the TRF1 C terminus and a noncanomical DNA binding surface on TRF1 are critical for its association with telomeric nucleosomes. These insights into shelterin-chromatin interactions have crucial implications for understanding telomeric chromatin organization and other roles of shelterin at telomeres including replication and transcription. | ||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8ox1.cif.gz | 366.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8ox1.ent.gz | 271 KB | Display | PDB format |
PDBx/mmJSON format | 8ox1.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8ox1_validation.pdf.gz | 1.4 MB | Display | wwPDB validaton report |
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Full document | 8ox1_full_validation.pdf.gz | 1.4 MB | Display | |
Data in XML | 8ox1_validation.xml.gz | 47.2 KB | Display | |
Data in CIF | 8ox1_validation.cif.gz | 74.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ox/8ox1 ftp://data.pdbj.org/pub/pdb/validation_reports/ox/8ox1 | HTTPS FTP |
-Related structure data
Related structure data | 17252MC 8ox0C 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
-Protein , 4 types, 8 molecules AEBFCGDH
#1: Protein | Mass: 15805.581 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) Gene: H3C1, H3FA, HIST1H3A, H3C2, H3FL, HIST1H3B, H3C3, H3FC HIST1H3C, H3C4, H3FB, HIST1H3D, H3C6, H3FD, HIST1H3E, H3C7, H3FI, HIST1H3F, H3C8, H3FH, HIST1H3G, H3C10, H3FK, HIST1H3H, H3C11, H3FF, ...Gene: H3C1, H3FA, HIST1H3A, H3C2, H3FL, HIST1H3B, H3C3, H3FC HIST1H3C, H3C4, H3FB, HIST1H3D, H3C6, H3FD, HIST1H3E, H3C7, H3FI, HIST1H3F, H3C8, H3FH, HIST1H3G, H3C10, H3FK, HIST1H3H, H3C11, H3FF, HIST1H3I, H3C12, H3FJ, HIST1H3J Production host: Escherichia coli (E. coli) / References: UniProt: P68431 #2: Protein | Mass: 11762.839 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) Gene: H4C1, H4/A, H4FA, HIST1H4A, H4C2, H4/I, H4FI, HIST1H4B, H4C3, H4/G, H4FG, HIST1H4C, H4C4, H4/B, H4FB, HIST1H4D, H4C5, H4/J, H4FJ, HIST1H4E, H4C6, H4/C, H4FC, HIST1H4F, H4C8, H4/H, H4FH, ...Gene: H4C1, H4/A, H4FA, HIST1H4A, H4C2, H4/I, H4FI, HIST1H4B, H4C3, H4/G, H4FG, HIST1H4C, H4C4, H4/B, H4FB, HIST1H4D, H4C5, H4/J, H4FJ, HIST1H4E, H4C6, H4/C, H4FC, HIST1H4F, H4C8, H4/H, H4FH, HIST1H4H, H4C9, H4/M, H4FM, HIST1H4I, H4C11, H4/E, H4FE, HIST1H4J, H4C12, H4/D, H4FD, HIST1H4K, H4C13, H4/K, H4FK, HIST1H4L, H4C14, H4/N, H4F2, H4FN, HIST2H4, HIST2H4A, H4C15, H4/O, H4FO, HIST2H4B, H4C16, H4-16, HIST4H4 Production host: Escherichia coli (E. coli) / References: UniProt: P62805 #3: Protein | Mass: 14503.938 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: H2AC6, H2AFL, HIST1H2AC / Production host: Escherichia coli (E. coli) / References: UniProt: Q93077 #4: Protein | Mass: 14305.627 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) Gene: H2BC4, H2BFL, HIST1H2BC, H2BC6, H2BFH, HIST1H2BE, H2BC7, H2BFG, HIST1H2BF, H2BC8, H2BFA, HIST1H2BG, H2BC10, H2BFK, HIST1H2BI Production host: Escherichia coli (E. coli) / References: UniProt: P62807 |
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-Telomeric DNA ... , 2 types, 2 molecules IJ
#5: DNA chain | Mass: 43478.914 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Escherichia coli (E. coli) |
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#6: DNA chain | Mass: 46024.258 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Escherichia coli (E. coli) |
-Telomeric repeat-binding factor ... , 2 types, 2 molecules LM
#7: Protein | Mass: 50322.641 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: TERF1, PIN2, TRBF1, TRF, TRF1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P54274 |
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#8: Protein | Mass: 50562.570 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: TERF1, PIN2, TRBF1, TRF, TRF1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P54274 |
-Non-polymers , 1 types, 11 molecules
#9: Water | ChemComp-HOH / |
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-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 |
-Sample preparation
Component |
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Molecular weight |
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Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 8 Details: 25 mM HEPES-KOH pH 8.0, 150 mM KCl, 1 mM MgCl2, 1% glycerol, 0.01% Igepal CA-630, 1 mM DTT | |||||||||||||||||||||||||||||||||||
Buffer component |
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Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | |||||||||||||||||||||||||||||||||||
Specimen support | Grid material: COPPER / Grid mesh size: 300 divisions/in. / Grid type: C-flat-1.2/1.3 | |||||||||||||||||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277.15 K / Details: Blot Force: -15 Blot Time: 2.5 s |
-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: 2500 nm / Nominal defocus min: 1000 nm / Cs: 2.7 mm / C2 aperture diameter: 50 µm / Alignment procedure: COMA FREE |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Temperature (min): 78 K |
Image recording | Average exposure time: 2.25 sec. / Electron dose: 56 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) / Num. of grids imaged: 1 / Num. of real images: 24566 |
EM imaging optics | Energyfilter name: GIF Quantum LS / Energyfilter slit width: 20 eV |
-Processing
EM software |
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Image processing | Details: All images were processed using RELION4.0 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 5031654 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 2.7 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 93463 / Num. of class averages: 1 / Symmetry type: POINT | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement | Resolution: 2.7→125.55 Å / Cor.coef. Fo:Fc: 0.879 / SU B: 10.283 / SU ML: 0.19 / ESU R: 0.313 Stereochemistry target values: MAXIMUM LIKELIHOOD WITH PHASES Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 107.728 Å2
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Refinement step | Cycle: 1 / Total: 13191 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
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