8a2q | pdb_00008a2q

Structure of the DNA-bound FANCD2-FANCI complex containing phosphomimetic FANCI

spinqualitylabelsall models 8a2q, resolution 3.53Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8a2q is a 4 chain structure with sequence from Gallus gallus and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.53Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function B0I564_CHICK Publication Abstract from PubMed DNA interstrand cross-links are tumor-inducing lesions that block DNA replication and transcription. When cross-links are detected at stalled replication forks, ATR kinase phosphorylates FANCI, which stimulates monoubiquitination of the FANCD2-FANCI clamp by the Fanconi anemia core complex. Monoubiquitinated FANCD2-FANCI is locked onto DNA and recruits nucleases that mediate DNA repair. However, it remains unclear how phosphorylation activates this pathway. Here, we report structures of FANCD2-FANCI complexes containing phosphomimetic FANCI. We observe that, unlike wild-type FANCD2-FANCI, the phosphomimetic complex closes around DNA, independent of the Fanconi anemia core complex. The phosphomimetic mutations do not substantially alter DNA binding but instead destabilize the open state of FANCD2-FANCI and alter its conformational dynamics. Overall, our results demonstrate that phosphorylation primes the FANCD2-FANCI clamp for ubiquitination, showing how multiple posttranslational modifications are coordinated to control DNA repair. The DNA-damage kinase ATR activates the FANCD2-FANCI clamp by priming it for ubiquitination.,Sijacki T, Alcon P, Chen ZA, McLaughlin SH, Shakeel S, Rappsilber J, Passmore LA Nat Struct Mol Biol. 2022 Sep;29(9):881-890. doi: 10.1038/s41594-022-00820-9. , Epub 2022 Sep 1. PMID:36050501 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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