7TUJ
NMR solution structure of the phosphorylated MUS81-binding region from human SLX4
Summary for 7TUJ
Entry DOI | 10.2210/pdb7tuj/pdb |
Related | 6VWB |
NMR Information | BMRB: 30986 |
Descriptor | Structure-specific endonuclease subunit SLX4 (1 entity in total) |
Functional Keywords | sap domain, disorder-to-order transition, protein binding |
Biological source | Homo sapiens (human) |
Total number of polymer chains | 1 |
Total formula weight | 9956.20 |
Authors | Payliss, B.J.,Reichheld, S.E.,Lemak, A.,Arrowsmith, C.H.,Sharpe, S.,Wyatt, H.D.M. (deposition date: 2022-02-02, release date: 2022-10-19, Last modification date: 2022-11-09) |
Primary citation | 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 Cited by 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: 36288699DOI: 10.1016/j.celrep.2022.111537 PDB entries with the same primary citation |
Experimental method | SOLUTION NMR |
Structure validation
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