6tng

Structure of FANCD2 in complex with FANCI

Loading... Status: waiting for Mol* initialization Structural highlights 6tng is a 2 chain structure with sequence from Gallus gallus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 4.1Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function F1NP22_CHICK Publication Abstract from PubMed Vertebrate DNA crosslink repair excises toxic replication-blocking DNA crosslinks. Numerous factors involved in crosslink repair have been identified, and mutations in their corresponding genes cause Fanconi anemia (FA). A key step in crosslink repair is monoubiquitination of the FANCD2-FANCI heterodimer, which then recruits nucleases to remove the DNA lesion. Here, we use cryo-EM to determine the structures of recombinant chicken FANCD2 and FANCI complexes. FANCD2-FANCI adopts a closed conformation when the FANCD2 subunit is monoubiquitinated, creating a channel that encloses double-stranded DNA (dsDNA). Ubiquitin is positioned at the interface of FANCD2 and FANCI, where it acts as a covalent molecular pin to trap the complex on DNA. In contrast, isolated FANCD2 is a homodimer that is unable to bind DNA, suggestive of an autoinhibitory mechanism that prevents premature activation. Together, our work suggests that FANCD2-FANCI is a clamp that is locked onto DNA by ubiquitin, with distinct interfaces that may recruit other DNA repair factors. FANCD2-FANCI is a clamp stabilized on DNA by monoubiquitination of FANCD2 during DNA repair.,Alcon P, Shakeel S, Chen ZA, Rappsilber J, Patel KJ, Passmore LA Nat Struct Mol Biol. 2020 Feb 17. pii: 10.1038/s41594-020-0380-1. doi:, 10.1038/s41594-020-0380-1. PMID:32066963 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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