Crystal structure of the SLF1 tandem BRCT domains in complex with a RPB2-derived peptide.

The tandem BRCT domains in the SMC5/6 complex localization factor 1 (SLF1, SLF1tBRCT) mediate interactions with a phosphorylated region in Rad18 and interaction targets the SMC5/6 complex to DNA damage sites for repair. Whether SLF1tBRCT mediate interactions with additional proteins is unclear. In this study, we searched for novel SLF1tBRCT binding partners and found that RNA polymerase II subunit 2 (RPB2) may contain a SLF1tBRCT binding site. The crystal structure of SLF1tBRCT in complex with a RPB2 peptide containing the predicted binding site revealed a SLF1tBRCT-RPB2 interface that bares similarity to the previously reported SLF1tBRCT-Rad18 interface but contains several unique features. Importantly, the SLF1tBRCT BRCT2 domain undergoes conformational changes to accommodate the C-terminus of the RPB2 peptide. Interestingly, this domain also mediates domain-swapping interactions between neighboring SLF1tBRCT molecules in the crystal. Our study suggests that RPB2 may be a potential SLF1 binding partner and provides insights into the structural flexibility of SLF1tBRCT.