- EMDB-23085: Structure of the human Fanconi anaemia Core complex -
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Basic information
Entry
Database: EMDB / ID: EMD-23085
Title
Structure of the human Fanconi anaemia Core complex
Map data
composite REFMAC5 map (masked) used in coordinate refinement
Sample
Complex: Human Fanconi Anaemia Core complex
Protein or peptide: Fanconi anemia group A protein
Protein or peptide: Fanconi anemia group B protein
Protein or peptide: Fanconi anemia group C protein
Protein or peptide: Fanconi anemia group E protein
Protein or peptide: Fanconi anemia group F protein
Protein or peptide: Fanconi anemia group G protein
Protein or peptide: E3 ubiquitin-protein ligase FANCL
Protein or peptide: Fanconi anemia core complex-associated protein 100
Protein or peptide: Fanconi anemia core complex-associated protein 20
Ligand: ZINC ION
Keywords
Complex / LIGASE
Function / homology
Function and homology information
regulation of germ cell proliferation / regulation of CD40 signaling pathway / Fanconi anaemia nuclear complex / regulation of regulatory T cell differentiation / male meiotic nuclear division / gamete generation / neuronal stem cell population maintenance / replication-born double-strand break repair via sister chromatid exchange / brain morphogenesis / myeloid cell homeostasis ...regulation of germ cell proliferation / regulation of CD40 signaling pathway / Fanconi anaemia nuclear complex / regulation of regulatory T cell differentiation / male meiotic nuclear division / gamete generation / neuronal stem cell population maintenance / replication-born double-strand break repair via sister chromatid exchange / brain morphogenesis / myeloid cell homeostasis / female gonad development / spermatid development / germ cell development / homeostasis of number of cells / protein monoubiquitination / negative regulation of double-strand break repair via homologous recombination / positive regulation of double-strand break repair via homologous recombination / interstrand cross-link repair / ovarian follicle development / removal of superoxide radicals / nucleotide-excision repair / mitochondrion organization / TP53 Regulates Transcription of DNA Repair Genes / Fanconi Anemia Pathway / response to radiation / RING-type E3 ubiquitin transferase / PKR-mediated signaling / male gonad development / ubiquitin-protein transferase activity / ubiquitin protein ligase activity / nuclear envelope / regulation of cell population proliferation / chromosome / cellular response to oxidative stress / protein-containing complex assembly / regulation of inflammatory response / gene expression / damaged DNA binding / nuclear speck / nuclear body / DNA repair / intracellular membrane-bounded organelle / centrosome / ubiquitin protein ligase binding / DNA damage response / chromatin / mitochondrion / DNA binding / zinc ion binding / nucleoplasm / nucleus / cytosol / cytoplasm Similarity search - Function
Fanconi anaemia group C protein / Fanconi anemia-associated protein of 100kDa / Fanconi anemia group B protein / Fanconi anemia group G protein / Fanconi anaemia group C protein / Fanconi anemia-associated / Fanconi Anaemia group E protein, C-terminal / Fanconi anemia group F protein / FANCF, C-terminal domain superfamily / Fanconi anemia group E protein ...Fanconi anaemia group C protein / Fanconi anemia-associated protein of 100kDa / Fanconi anemia group B protein / Fanconi anemia group G protein / Fanconi anaemia group C protein / Fanconi anemia-associated / Fanconi Anaemia group E protein, C-terminal / Fanconi anemia group F protein / FANCF, C-terminal domain superfamily / Fanconi anemia group E protein / Fanconi anemia group F protein (FANCF) / Fanconi Anaemia group E protein FANCE / Fanconi anaemia group A protein / Fanconi anaemia group A protein, N-terminal domain / : / : / : / Fanconi anaemia group A protein C-terminal domain / Fanconi anaemia group A protein N terminus / FANCA helical domain / FANCA arcN subdomain / Fanconi anemia complex, subunit FancL, WD-repeat containing domain / E3 ubiquitin-protein ligase FANCL / FANCL C-terminal domain / FANCL, UBC-like domain 3 superfamily / FANCL, UBC-like domain 2 / FANCL, UBC-like domain 3 / FANCL UBC-like domain 1 / FANCL C-terminal domain / FANCL UBC-like domain 2 / FANCL UBC-like domain 3 / FANCL C-terminal domain / Ubiquitin-conjugating enzyme/RWD-like / Tetratricopeptide repeats / Tetratricopeptide repeat / Tetratricopeptide-like helical domain superfamily / Zinc finger, RING/FYVE/PHD-type Similarity search - Domain/homology
Fanconi anemia group G protein / Fanconi anemia group A protein / Fanconi anemia group C protein / Fanconi anemia core complex-associated protein 100 / Fanconi anemia group B protein / Fanconi anemia group E protein / Fanconi anemia group F protein / E3 ubiquitin-protein ligase FANCL Similarity search - Component
Biological species
Homo sapiens (human)
Method
single particle reconstruction / cryo EM / Resolution: 3.1 Å
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
Deposition
Dec 10, 2020
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Header (metadata) release
Mar 10, 2021
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Map release
Mar 10, 2021
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Update
Mar 6, 2024
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Current status
Mar 6, 2024
Processing site: RCSB / Status: Released
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Structure visualization
Movie
Surface view with section colored by density value
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