7TUJ

NMR solution structure of the phosphorylated MUS81-binding region from human SLX4

7TUJ の概要

• エントリーDOI: 10.2210/pdb7tuj/pdb
• 関連するPDBエントリー: 6VWB
• NMR情報: BMRB: 30986
• 分子名称: Structure-specific endonuclease subunit SLX4 (1 entity in total)
• 機能のキーワード: sap domain, disorder-to-order transition, protein binding
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 9956.20

構造登録者

Payliss, B.J.,Reichheld, S.E.,Lemak, A.,Arrowsmith, C.H.,Sharpe, S.,Wyatt, H.D.M. (登録日: 2022-02-02, 公開日: 2022-10-19, 最終更新日: 2022-11-09)

主引用文献

Payliss, B.J.,Tse, Y.W.E.,Reichheld, S.E.,Lemak, A.,Yun, H.Y.,Houliston, S.,Patel, A.,Arrowsmith, C.H.,Sharpe, S.,Wyatt, H.D.M.
Phosphorylation of the DNA repair scaffold SLX4 drives folding of the SAP domain and activation of the MUS81-EME1 endonuclease.
Cell Rep, 41:111537-111537, 2022

PubMed Abstract: The DNA repair scaffold SLX4 has multifaceted roles in genome stability, many of which depend on structure-selective endonucleases. SLX4 coordinates the cell cycle-regulated assembly of SLX1, MUS81-EME1, and XPF-ERCC1 into a tri-nuclease complex called SMX. Mechanistically, how the mitotic kinase CDK1 regulates the interaction between SLX4 and MUS81-EME1 remains unclear. Here, we show that CDK1-cyclin B phosphorylates SLX4 residues T1544, T1561, and T1571 in the MUS81-binding region (SLX4). Phosphorylated SLX4 relaxes the substrate specificity of MUS81-EME1 and stimulates cleavage of replication and recombination structures, providing a biochemical explanation for the chromosome pulverization that occurs when SLX4 binds MUS81 in S-phase. Remarkably, phosphorylation of SLX4 drives folding of an SAP domain, which underpins the high-affinity interaction with MUS81. We also report the structure of phosphorylated SLX4 and identify the MUS81-binding interface. Our work provides mechanistic insights into how cell cycle-regulated phosphorylation of SLX4 drives the recruitment and activation of MUS81-EME1.

PubMed: 36288699
DOI: 10.1016/j.celrep.2022.111537

実験手法

SOLUTION NMR