8A2Q

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

8A2Q の概要

• エントリーDOI: 10.2210/pdb8a2q/pdb
• EMDBエントリー: 15101 15102 15103
• 分子名称: FANCD2, Fanconi anemia complementation group I, DNA (29-MER), ... (4 entities in total)
• 機能のキーワード: nucleic acid protein complex, dna clamp, solenoid domains, fanconi anemia, dna repair, dna damage, dna inter strand crosslink, dna binding protein, ubiquitination, atr, pathway activation
• 由来する生物種: Gallus gallus (chicken); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 342184.91

構造登録者

Passmore, L.A.,Sijacki, T.,Alcon, P. (登録日: 2022-06-06, 公開日: 2022-09-07, 最終更新日: 2024-07-24)

主引用文献

Sijacki, T.,Alcon, P.,Chen, Z.A.,McLaughlin, S.H.,Shakeel, S.,Rappsilber, J.,Passmore, L.A.
The DNA-damage kinase ATR activates the FANCD2-FANCI clamp by priming it for ubiquitination.
Nat.Struct.Mol.Biol., 29:881-890, 2022

PubMed Abstract: 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.

PubMed: 36050501
DOI: 10.1038/s41594-022-00820-9

実験手法

ELECTRON MICROSCOPY (3.53 Å)