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Yorodumi- PDB-7kzv: Structure of the human fanconi anaemia Core-UBE2T-ID-DNA complex ... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7kzv | ||||||
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Title | Structure of the human fanconi anaemia Core-UBE2T-ID-DNA complex in closed state | ||||||
Components |
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Keywords | LIGASE/DNA / Complex / LIGASE / LIGASE-DNA complex | ||||||
Function / homology | Function and homology information regulation of germ cell proliferation / regulation of CD40 signaling pathway / protein K29-linked ubiquitination / Fanconi anaemia nuclear complex / protein K27-linked ubiquitination / regulation of regulatory T cell differentiation / homologous chromosome pairing at meiosis / double-strand break repair involved in meiotic recombination / male meiotic nuclear division / gamete generation ...regulation of germ cell proliferation / regulation of CD40 signaling pathway / protein K29-linked ubiquitination / Fanconi anaemia nuclear complex / protein K27-linked ubiquitination / regulation of regulatory T cell differentiation / homologous chromosome pairing at meiosis / double-strand break repair involved in meiotic recombination / male meiotic nuclear division / gamete generation / replication-born double-strand break repair via sister chromatid exchange / neuronal stem cell population maintenance / protein K6-linked ubiquitination / protein K11-linked ubiquitination / brain morphogenesis / DNA repair complex / mitotic intra-S DNA damage checkpoint signaling / E2 ubiquitin-conjugating enzyme / myeloid cell homeostasis / negative regulation of double-strand break repair via homologous recombination / positive regulation of double-strand break repair via homologous recombination / female gonad development / protein monoubiquitination / ubiquitin conjugating enzyme activity / spermatid development / germ cell development / protein K63-linked ubiquitination / protein K48-linked ubiquitination / protein autoubiquitination / interstrand cross-link repair / DNA polymerase binding / ovarian follicle development / condensed chromosome / removal of superoxide radicals / mitochondrion organization / Synthesis of active ubiquitin: roles of E1 and E2 enzymes / nucleotide-excision repair / Fanconi Anemia Pathway / TP53 Regulates Transcription of DNA Repair Genes / response to gamma radiation / RING-type E3 ubiquitin transferase / response to radiation / PKR-mediated signaling / protein polyubiquitination / ubiquitin-protein transferase activity / male gonad development / ubiquitin protein ligase activity / cellular response to oxidative stress / nuclear envelope / chromosome / regulation of cell population proliferation / regulation of inflammatory response / protein-containing complex assembly / damaged DNA binding / nuclear body / intracellular membrane-bounded organelle / DNA repair / centrosome / DNA damage response / ubiquitin protein ligase binding / chromatin binding / chromatin / nucleolus / mitochondrion / DNA binding / nucleoplasm / ATP binding / metal ion binding / nucleus / plasma membrane / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) synthetic construct (others) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.2 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 |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7kzv.cif.gz | 8.3 MB | Display | PDBx/mmCIF format |
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PDB format | pdb7kzv.ent.gz | Display | PDB format | |
PDBx/mmJSON format | 7kzv.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/kz/7kzv ftp://data.pdbj.org/pub/pdb/validation_reports/kz/7kzv | HTTPS FTP |
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-Related structure data
Related structure data | 23090MC 7kzpC 7kzqC 7kzrC 7kzsC 7kztC 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 #12: 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 LMXU
#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: 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 #11: 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 |
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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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-DNA chain , 2 types, 2 molecules YZ
#13: DNA chain | Mass: 18036.518 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others) |
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#14: DNA chain | Mass: 17716.326 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others) |
-Non-polymers , 1 types, 5 molecules
#15: Chemical | ChemComp-ZN / |
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-Details
Has ligand of interest | N |
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Sequence details | The complete FAAP20 sequence is MEAARRPRLGLSRRRPPPAGGPSGGRPWFLLGGDERERLWAELLRTVSPELILDHEVPSL ...The complete FAAP20 sequence 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-DNA complex / Type: COMPLEX / Entity ID: #1-#14 / 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 FIELDBright-field microscopy |
Image recording | Electron dose: 36.5 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K3 (6k 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: 4.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 74481 / Symmetry type: POINT | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement | Resolution: 4.2→40 Å / Cor.coef. Fo:Fc: 0.906 / SU B: 91.931 / SU ML: 0.487 / ESU R: 0.777 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: 94.302 Å2
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Refinement step | Cycle: 1 / Total: 88227 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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