Structural insights into Rad18 targeting by the SLF1 BRCT domains Journal Article
| Authors: | Huang, W.; Qiu, F.; Zheng, L.; Shi, M.; Shen, M.; Zhao, X.; Xiang, S. |
| Article Title: | Structural insights into Rad18 targeting by the SLF1 BRCT domains |
| Abstract: | Rad18 interacts with the SMC5/6 localization factor 1 (SLF1) to recruit the SMC5/6 complex to DNA damage sites for repair. The mechanism of the specific Rad18 recognition by SLF1 is unclear. Here, we present the crystal structure of the tandem BRCT repeat (tBRCT) in SLF1 (SLF1tBRCT) bound with the interacting Rad18 peptide. Our structure and biochemical studies demonstrate that SLF1tBRCT interacts with two phosphoserines and adjacent residues in Rad18 for high-affinity and specificity Rad18 recognition. We found that SLF1tBRCT utilizes mechanisms common among tBRCTs as well as unique ones for Rad18 binding, the latter include interactions with an α-helical structure in Rad18 that has not been observed in other tBRCT-bound ligand proteins. Our work provides structural insights into Rad18 targeting by SLF1 and expands the understanding of BRCT-mediated complex assembly. © 2023 The Authors |
| Keywords: | proteins; phosphorylation; dna damage response; crystal structure; x ray crystallography; x-ray crystallography; protein-protein interactions; dna damages; protein-protein interaction; protein complex; structural insights; protein complexes; smc5/6 complex; rad18; slf1; localization factor; smc5/6 localization factor 1 |
| Journal Title: | Journal of Biological Chemistry |
| Volume: | 299 |
| Issue: | 11 |
| ISSN: | 0021-9258 |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| Date Published: | 2023-11-01 |
| Start Page: | 105288 |
| Language: | English |
| DOI: | 10.1016/j.jbc.2023.105288 |
| PUBMED: | 37748650 |
| PROVIDER: | scopus |
| PMCID: | PMC10598736 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PubMed record -- Source: Scopus |
