A comparative study of protein–ssDNA interactions

Abstract

Abstract Single-stranded DNA-binding proteins (SSBs) play crucial roles in DNA replication, recombination and repair, and serve as key players in the maintenance of genomic stability. While a number of SSBs bind single-stranded DNA (ssDNA) non-specifically, the others recognize and bind specific ssDNA sequences. The mechanisms underlying this binding discrepancy, however, are largely unknown. Here, we present a comparative study of protein–ssDNA interactions by annotating specific and non-specific SSBs and comparing structural features such as DNA-binding propensities and secondary structure types of residues in SSB–ssDNA interactions, protein–ssDNA hydrogen bonding and π–π interactions between specific and non-specific SSBs. Our results suggest that protein side chain-DNA base hydrogen bonds are the major contributors to protein–ssDNA binding specificity, while π–π interactions may mainly contribute to binding affinity. We also found the enrichment of aspartate in the specific SSBs, a key feature in specific protein–double-stranded DNA (dsDNA) interactions as reported in our previous study. In addition, no significant differences between specific and non-specific groups with respect of conformational changes upon ssDNA binding were found, suggesting that the flexibility of SSBs plays a lesser role than that of dsDNA-binding proteins in conferring binding specificity.