+Open data
-Basic information
Entry | Database: PDB / ID: 7kzr | ||||||
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Title | Structure of the human Fanconi Anaemia Core-UBE2T-ID complex | ||||||
Components |
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Keywords | LIGASE / Complex | ||||||
Function / homology | Function and homology information regulation of germ cell proliferation / regulation of CD40 signaling pathway / Fanconi anaemia nuclear complex / protein K27-linked ubiquitination / protein K29-linked ubiquitination / regulation of regulatory T cell differentiation / homologous chromosome pairing at meiosis / male meiotic nuclear division / gamete generation / double-strand break repair involved in meiotic recombination ...regulation of germ cell proliferation / regulation of CD40 signaling pathway / Fanconi anaemia nuclear complex / protein K27-linked ubiquitination / protein K29-linked ubiquitination / regulation of regulatory T cell differentiation / homologous chromosome pairing at meiosis / male meiotic nuclear division / gamete generation / double-strand break repair involved in meiotic recombination / neuronal stem cell population maintenance / replication-born double-strand break repair via sister chromatid exchange / protein K6-linked ubiquitination / brain morphogenesis / protein K11-linked ubiquitination / DNA repair complex / mitotic intra-S DNA damage checkpoint signaling / myeloid cell homeostasis / E2 ubiquitin-conjugating enzyme / female gonad development / protein monoubiquitination / germ cell development / ubiquitin conjugating enzyme activity / protein K63-linked ubiquitination / spermatid development / positive regulation of double-strand break repair via homologous recombination / protein autoubiquitination / protein K48-linked ubiquitination / negative regulation of double-strand break repair via homologous recombination / interstrand cross-link repair / ovarian follicle development / DNA polymerase binding / condensed chromosome / removal of superoxide radicals / Synthesis of active ubiquitin: roles of E1 and E2 enzymes / mitochondrion organization / TP53 Regulates Transcription of DNA Repair Genes / nucleotide-excision repair / response to gamma radiation / Fanconi Anemia Pathway / response to radiation / PKR-mediated signaling / protein polyubiquitination / ubiquitin-protein transferase activity / male gonad development / chromosome / cellular response to oxidative stress / regulation of inflammatory response / protein-containing complex assembly / damaged DNA binding / nuclear body / DNA repair / centrosome / ubiquitin protein ligase binding / DNA damage response / chromatin binding / chromatin / nucleolus / mitochondrion / DNA binding / nucleoplasm / ATP binding / nucleus / plasma membrane / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.4 Å | ||||||
Authors | Wang, S.L. / Pavletich, N.P. | ||||||
Funding support | United States, 1items
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Citation | Journal: Nat Struct Mol Biol / Year: 2021 Title: Structure of the FA core ubiquitin ligase closing the ID clamp on DNA. Authors: Shengliu Wang / Renjing Wang / Christopher Peralta / Ayat Yaseen / Nikola P Pavletich / Abstract: The Fanconi anemia (FA) pathway is essential for the repair of DNA interstrand crosslinks. Central to the pathway is the FA core complex, a ubiquitin ligase of nine subunits that monoubiquitinates ...The Fanconi anemia (FA) pathway is essential for the repair of DNA interstrand crosslinks. Central to the pathway is the FA core complex, a ubiquitin ligase of nine subunits that monoubiquitinates the FANCI-FANCD2 (ID) DNA clamp. The 3.1 Å structure of the 1.1-MDa human FA core complex, described here, reveals an asymmetric assembly with two copies of all but the FANCC, FANCE and FANCF subunits. The asymmetry is crucial, as it prevents the binding of a second FANCC-FANCE-FANCF subcomplex that inhibits the recruitment of the UBE2T ubiquitin conjugating enzyme, and instead creates an ID binding site. A single active site then ubiquitinates FANCD2 and FANCI sequentially. We also present the 4.2-Å structures of the human core-UBE2T-ID-DNA complex in three conformations captured during monoubiquitination. They reveal the core-UBE2T complex remodeling the ID-DNA complex, closing the clamp on the DNA before ubiquitination. Monoubiquitination then prevents clamp opening after release from the core. | ||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7kzr.cif.gz | 8.1 MB | Display | PDBx/mmCIF format |
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PDB format | pdb7kzr.ent.gz | Display | PDB format | |
PDBx/mmJSON format | 7kzr.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7kzr_validation.pdf.gz | 936.8 KB | Display | wwPDB validaton report |
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Full document | 7kzr_full_validation.pdf.gz | 1 MB | Display | |
Data in XML | 7kzr_validation.xml.gz | 258.7 KB | Display | |
Data in CIF | 7kzr_validation.cif.gz | 410.2 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/kz/7kzr ftp://data.pdbj.org/pub/pdb/validation_reports/kz/7kzr | HTTPS FTP |
-Related structure data
Related structure data | 23087MC 7kzpC 7kzqC 7kzsC 7kztC 7kzvC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Fanconi anemia group ... , 7 types, 10 molecules ASBOCEFGHV
#1: Protein | Mass: 165513.016 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: FANCA, FAA, FACA, FANCH / Production host: Homo sapiens (human) / References: UniProt: O15360 #2: Protein | Mass: 100640.172 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: FANCB / Production host: Homo sapiens (human) / References: UniProt: Q8NB91 #3: Protein | | Mass: 66290.359 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: FANCC, FAC, FACC / Production host: Homo sapiens (human) / References: UniProt: Q00597 #4: Protein | | Mass: 61026.086 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: FANCE, FACE / Production host: Homo sapiens (human) / References: UniProt: Q9HB96 #5: Protein | | Mass: 45108.297 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: FANCF / Production host: Homo sapiens (human) / References: UniProt: Q9NPI8 #6: Protein | Mass: 70873.727 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: FANCG, XRCC9 / Production host: Homo sapiens (human) / References: UniProt: O15287 #11: Protein | | Mass: 164325.516 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: FANCD2, FACD / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q9BXW9 |
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-Protein , 3 types, 4 molecules LMUX
#7: Protein | Mass: 45203.953 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: FANCL, PHF9 / Production host: Homo sapiens (human) References: UniProt: Q9NW38, RING-type E3 ubiquitin transferase #10: Protein | | Mass: 149512.078 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: FANCI / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: B7ZMF2 #12: Protein | | Mass: 22553.873 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: UBE2T, HSPC150, PIG50 / Production host: Escherichia coli (E. coli) References: UniProt: Q9NPD8, E2 ubiquitin-conjugating enzyme |
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-Fanconi anemia core complex-associated protein ... , 2 types, 3 molecules PQW
#8: Protein | Mass: 96513.898 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: FAAP100, C17orf70 / Production host: Homo sapiens (human) / References: UniProt: Q0VG06 #9: Protein/peptide | | Mass: 4041.667 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) |
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-Non-polymers , 1 types, 5 molecules
#13: Chemical | ChemComp-ZN / |
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-Details
Has ligand of interest | N |
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Sequence details | The complete sequence of FAAP20 is MEAARRPRLGLSRRRPPPAGGPSGGRPWFLLGGDERERLWAELLRTVSPELILDHEVPSL ...The complete sequence of FAAP20 is MEAARRPRLG |
-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: Human Fanconi Anaemia Core-UBE2T-ID complex / Type: COMPLEX / Entity ID: #1-#12 / Source: RECOMBINANT | ||||||||||||||||||||
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Molecular weight | Value: 1.4 MDa / Experimental value: NO | ||||||||||||||||||||
Source (natural) | Organism: Homo sapiens (human) | ||||||||||||||||||||
Source (recombinant) | Organism: Homo sapiens (human) | ||||||||||||||||||||
Buffer solution | pH: 8 | ||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 1 mg/ml / 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 |
Image recording | Electron dose: 60 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
Software | Name: REFMAC / Version: 5.8.0267 / Classification: refinement | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 4.4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 114249 / Symmetry type: POINT | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement | Resolution: 4.4→4.4 Å / Cor.coef. Fo:Fc: 0.967 / SU B: 114.471 / SU ML: 0.615 / ESU R: 0.735 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: 0.9 Å / Shrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: MASK | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 79.835 Å2
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Refinement step | Cycle: 1 / Total: 86745 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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