4P0P

Crystal structure of Human Mus81-Eme1 in complex with 5'-flap DNA, and Mg2+

4P0P の概要

• エントリーDOI: 10.2210/pdb4p0p/pdb
• 関連するPDBエントリー: 4P0Q 4P0R 4P0S
• 分子名称: Crossover junction endonuclease MUS81, Crossover junction endonuclease EME1, DNA GAATGTGTGTCTCAATC, ... (7 entities in total)
• 機能のキーワード: resolvase, hydroase-dna complex, hydrolase-dna complex, hydrolase/dna
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Nucleus, nucleolus : Q96NY9 Q96AY2
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 89697.80

構造登録者

Gwon, G.H.,Baek, K.,Cho, Y. (登録日: 2014-02-22, 公開日: 2014-05-28, 最終更新日: 2023-12-27)

主引用文献

Gwon, G.H.,Jo, A.,Baek, K.,Jin, K.S.,Fu, Y.,Lee, J.B.,Kim, Y.,Cho, Y.
Crystal structures of the structure-selective nuclease Mus81-Eme1 bound to flap DNA substrates.
Embo J., 33:1061-1072, 2014

PubMed Abstract: The Mus81-Eme1 complex is a structure-selective endonuclease with a critical role in the resolution of recombination intermediates during DNA repair after interstrand cross-links, replication fork collapse, or double-strand breaks. To explain the molecular basis of 3' flap substrate recognition and cleavage mechanism by Mus81-Eme1, we determined crystal structures of human Mus81-Eme1 bound to various flap DNA substrates. Mus81-Eme1 undergoes gross substrate-induced conformational changes that reveal two key features: (i) a hydrophobic wedge of Mus81 that separates pre- and post-nick duplex DNA and (ii) a "5' end binding pocket" that hosts the 5' nicked end of post-nick DNA. These features are crucial for comprehensive protein-DNA interaction, sharp bending of the 3' flap DNA substrate, and incision strand placement at the active site. While Mus81-Eme1 unexpectedly shares several common features with members of the 5' flap nuclease family, the combined structural, biochemical, and biophysical analyses explain why Mus81-Eme1 preferentially cleaves 3' flap DNA substrates with 5' nicked ends.

PubMed: 24733841
DOI: 10.1002/embj.201487820

実験手法

X-RAY DIFFRACTION (2.8 Å)