+Open data
-Basic information
Entry | Database: PDB / ID: 8vx6 | |||||||||
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Title | Human OGG1 bound at the nucleosomal DNA entry site | |||||||||
Components |
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Keywords | HYDROLASE / LYASE/STRUCTURAL PROTEIN/DNA / Nucleosome core particle containing 8-oxoG DNA damage / LYASE-STRUCTURAL PROTEIN-DNA complex | |||||||||
Function / homology | Function and homology information Defective OGG1 Substrate Binding / Defective OGG1 Substrate Processing / Defective OGG1 Localization / depurination / negative regulation of double-strand break repair via single-strand annealing / oxidized purine nucleobase lesion DNA N-glycosylase activity / base-excision repair, AP site formation / depyrimidination / 8-oxo-7,8-dihydroguanine DNA N-glycosylase activity / Displacement of DNA glycosylase by APEX1 ...Defective OGG1 Substrate Binding / Defective OGG1 Substrate Processing / Defective OGG1 Localization / depurination / negative regulation of double-strand break repair via single-strand annealing / oxidized purine nucleobase lesion DNA N-glycosylase activity / base-excision repair, AP site formation / depyrimidination / 8-oxo-7,8-dihydroguanine DNA N-glycosylase activity / Displacement of DNA glycosylase by APEX1 / positive regulation of gene expression via chromosomal CpG island demethylation / response to folic acid / oxidized purine DNA binding / Hydrolases; Glycosylases; Hydrolysing N-glycosyl compounds / APEX1-Independent Resolution of AP Sites via the Single Nucleotide Replacement Pathway / response to light stimulus / 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 / cellular response to cadmium ion / class I DNA-(apurinic or apyrimidinic site) endonuclease activity / DNA-(apurinic or apyrimidinic site) lyase / nucleotide-excision repair / response to radiation / base-excision repair / nuclear matrix / cellular response to reactive oxygen species / structural constituent of chromatin / nucleosome / nucleosome assembly / response to estradiol / microtubule binding / endonuclease activity / response to ethanol / response to oxidative stress / damaged DNA binding / nuclear speck / mitochondrial matrix / response to xenobiotic stimulus / protein heterodimerization activity / RNA polymerase II cis-regulatory region sequence-specific DNA binding / DNA damage response / regulation of DNA-templated transcription / negative regulation of apoptotic process / enzyme binding / positive regulation of transcription by RNA polymerase II / protein-containing complex / DNA binding / nucleoplasm / nucleus / cytosol Similarity search - Function | |||||||||
Biological species | Xenopus laevis (African clawed frog) Homo sapiens (human) synthetic construct (others) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.2 Å | |||||||||
Authors | You, Q. / Li, H. | |||||||||
Funding support | United States, 2items
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Citation | Journal: Commun Biol / Year: 2024 Title: Human 8-oxoguanine glycosylase OGG1 binds nucleosome at the dsDNA ends and the super-helical locations. Authors: Qinglong You / Xiang Feng / Yi Cai / Stephen B Baylin / Huilin Li / Abstract: The human glycosylase OGG1 extrudes and excises the oxidized DNA base 8-oxoguanine (8-oxoG) to initiate base excision repair and plays important roles in many pathological conditions such as cancer, ...The human glycosylase OGG1 extrudes and excises the oxidized DNA base 8-oxoguanine (8-oxoG) to initiate base excision repair and plays important roles in many pathological conditions such as cancer, inflammation, and neurodegenerative diseases. Previous structural studies have used a truncated protein and short linear DNA, so it has been unclear how full-length OGG1 operates on longer DNA or on nucleosomes. Here we report cryo-EM structures of human OGG1 bound to a 35-bp long DNA containing an 8-oxoG within an unmethylated Cp-8-oxoG dinucleotide as well as to a nucleosome with an 8-oxoG at super-helical location (SHL)-5. The 8-oxoG in the linear DNA is flipped out by OGG1, consistent with previous crystallographic findings with a 15-bp DNA. OGG1 preferentially binds near dsDNA ends at the nucleosomal entry/exit sites. Such preference may underlie the enzyme's function in DNA double-strand break repair. Unexpectedly, we find that OGG1 bends the nucleosomal entry DNA, flips an undamaged guanine, and binds to internal nucleosomal DNA sites such as SHL-5 and SHL+6. We suggest that the DNA base search mechanism by OGG1 may be chromatin context-dependent and that OGG1 may partner with chromatin remodelers to excise 8-oxoG at the nucleosomal internal sites. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8vx6.cif.gz | 399.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8vx6.ent.gz | 300.4 KB | Display | PDB format |
PDBx/mmJSON format | 8vx6.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8vx6_validation.pdf.gz | 1.1 MB | Display | wwPDB validaton report |
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Full document | 8vx6_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | 8vx6_validation.xml.gz | 42.7 KB | Display | |
Data in CIF | 8vx6_validation.cif.gz | 67.2 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/vx/8vx6 ftp://data.pdbj.org/pub/pdb/validation_reports/vx/8vx6 | HTTPS FTP |
-Related structure data
Related structure data | 43609MC 8vx4C 8vx5C 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
-DNA chain , 2 types, 2 molecules JI
#1: DNA chain | Mass: 51343.652 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others) |
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#2: DNA chain | Mass: 51785.953 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others) |
-Protein , 5 types, 9 molecules AEBFCGDHK
#3: Protein | Mass: 15435.126 Da / Num. of mol.: 2 / Mutation: G102A Source method: isolated from a genetically manipulated source Source: (gene. exp.) Xenopus laevis (African clawed frog) / Production host: Escherichia coli (E. coli) / References: UniProt: P84233 #4: Protein | Mass: 13307.514 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Xenopus laevis (African clawed frog) / Production host: Escherichia coli (E. coli) / References: UniProt: P62799 #5: Protein | Mass: 18086.951 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Xenopus laevis (African clawed frog) Gene: LOC494591, h2ac14.L, hist1h2aj, hist1h2aj.L, XELAEV_18003602mg Production host: Escherichia coli (E. coli) / References: UniProt: Q6AZJ8 #6: Protein | Mass: 13655.948 Da / Num. of mol.: 2 / Mutation: S29T Source method: isolated from a genetically manipulated source Source: (gene. exp.) Xenopus laevis (African clawed frog) / Production host: Escherichia coli (E. coli) / References: UniProt: P02281 #7: Protein | | Mass: 43720.020 Da / Num. of mol.: 1 / Mutation: K249Q Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: OGG1, MMH, MUTM, OGH1 / Production host: Escherichia coli (E. coli) References: UniProt: O15527, Hydrolases; Glycosylases; Hydrolysing N-glycosyl compounds, DNA-(apurinic or apyrimidinic site) lyase |
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-Details
Has ligand of interest | Y |
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Has protein modification | N |
-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 | Name: Complex of Human OGG1 with a 35 bp DNA duplex containing 8-oxoG Type: COMPLEX / Entity ID: #1-#6 / Source: RECOMBINANT |
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Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Escherichia coli (E. coli) |
Buffer solution | pH: 7.4 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-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 defocus max: 2000 nm / Nominal defocus min: 1000 nm / Cs: 2.7 mm / C2 aperture diameter: 100 µm |
Image recording | Electron dose: 64 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
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3D reconstruction | Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 142885 / Symmetry type: POINT | ||||||||||||||||||||||||
Atomic model building | Protocol: AB INITIO MODEL / Space: REAL | ||||||||||||||||||||||||
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