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TitleStructure of the FA core ubiquitin ligase closing the ID clamp on DNA.
Journal, issue, pagesNat Struct Mol Biol, Vol. 28, Issue 3, Page 300-309, Year 2021
Publish dateMar 8, 2021
AuthorsShengliu Wang / Renjing Wang / Christopher Peralta / Ayat Yaseen / Nikola P Pavletich /
PubMed AbstractThe 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.
External linksNat Struct Mol Biol / PubMed:33686268 / PubMed Central
MethodsEM (single particle)
Resolution3.1 - 4.4 Å
Structure data

23085

7kzp

EMDB-23085, PDB-7kzp:
Structure of the human Fanconi anaemia Core complex
Method: EM (single particle) / Resolution: 3.1 Å

23086

7kzq

EMDB-23086, PDB-7kzq:
Structure of the human Fanconi anaemia Core-ID complex
Method: EM (single particle) / Resolution: 4.3 Å

23087

7kzr

EMDB-23087, PDB-7kzr:
Structure of the human Fanconi Anaemia Core-UBE2T-ID complex
Method: EM (single particle) / Resolution: 4.4 Å

23088

7kzs

EMDB-23088, PDB-7kzs:
Structure of the human fanconi anaemia Core-UBE2T-ID-DNA complex in open state
Method: EM (single particle) / Resolution: 4.2 Å

23089

7kzt

EMDB-23089, PDB-7kzt:
Structure of the human fanconi anaemia Core-UBE2T-ID-DNA complex in intermediate state
Method: EM (single particle) / Resolution: 4.2 Å

23090

7kzv

EMDB-23090, PDB-7kzv:
Structure of the human fanconi anaemia Core-UBE2T-ID-DNA complex in closed state
Method: EM (single particle) / Resolution: 4.2 Å

Chemicals

ChemComp-ZN:
Unknown entry

Source
  • homo sapiens (human)
  • synthetic construct (others)
  • Human (human)
KeywordsLIGASE / Complex / LIGASE/DNA / LIGASE-DNA complex

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