4R8A

Crystal structure of paFAN1 - 5' flap DNA complex

4R8A の概要

• エントリーDOI: 10.2210/pdb4r8a/pdb
• 関連するPDBエントリー: 4R89
• 分子名称: Uncharacterized protein, DNA (5'-D(P*AP*CP*CP*AP*GP*AP*CP*AP*CP*AP*CP*AP*TP*TP*C)-3'), DNA (5'-D(P*GP*TP*TP*GP*GP*GP*AP*TP*TP*G)-3'), ... (5 entities in total)
• 機能のキーワード: dna binding, metal binding nuclease, 5'flap dna endo nuclease, fanconi anemia proteins family, hydrolase-dna complex, hydrolase/dna
• 由来する生物種: Pseudomonas aeruginosa; 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 157341.79

構造登録者

Cho, Y.,Gwon, G.H.,Kim, Y.R. (登録日: 2014-08-30, 公開日: 2014-10-29, 最終更新日: 2024-03-20)

主引用文献

Gwon, G.H.,Kim, Y.R.,Liu, Y.,Watson, A.T.,Jo, A.,Etheridge, T.J.,Yuan, F.,Zhang, Y.,Kim, Y.C.,Carr, A.M.,Cho, Y.
Crystal structure of a Fanconi anemia-associated nuclease homolog bound to 5' flap DNA: basis of interstrand cross-link repair by FAN1
Genes Dev., 28:2276-2290, 2014

PubMed Abstract: Fanconi anemia (FA) is an autosomal recessive genetic disorder caused by defects in any of 15 FA genes responsible for processing DNA interstrand cross-links (ICLs). The ultimate outcome of the FA pathway is resolution of cross-links, which requires structure-selective nucleases. FA-associated nuclease 1 (FAN1) is believed to be recruited to lesions by a monoubiquitinated FANCI-FANCD2 (ID) complex and participates in ICL repair. Here, we determined the crystal structure of Pseudomonas aeruginosa FAN1 (PaFAN1) lacking the UBZ (ubiquitin-binding zinc) domain in complex with 5' flap DNA. All four domains of the right-hand-shaped PaFAN1 are involved in DNA recognition, with each domain playing a specific role in bending DNA at the nick. The six-helix bundle that binds the junction connects to the catalytic viral replication and repair (VRR) nuclease (VRR nuc) domain, enabling FAN1 to incise the scissile phosphate a few bases distant from the junction. The six-helix bundle also inhibits the cleavage of intact Holliday junctions. PaFAN1 shares several conserved features with other flap structure-selective nucleases despite structural differences. A clamping motion of the domains around the wedge helix, which acts as a pivot, facilitates nucleolytic cleavage. The PaFAN1 structure provides insights into how archaeal Holliday junction resolvases evolved to incise 5' flap substrates and how FAN1 integrates with the FA complex to participate in ICL repair.

PubMed: 25319828
DOI: 10.1101/gad.248492.114

実験手法

X-RAY DIFFRACTION (3.2 Å)