Sodium Ion-Induced Structural Transition on the Surface of a DNA-Interacting Protein

Protein surfaces have pivotal roles in interactions between proteins and other biological molecules. However, the structural dynamics of protein surfaces have rarely been explored and are poorly understood. Here, the surface of a single-stranded DNA (ssDNA) binding protein (SSB) with four DNA binding domains that bind ssDNA in binding site sizes of 35, 56, and 65 nucleotides per tetramer is investigated. Using oligonucleotides as probes to sense the charged surface, NaCl induces a two-state structural transition on the SSB surface even at moderate concentrations. Chelation of sodium ions with charged amino acids alters the network of hydrogen bonds and/or salt bridges on the surface. Such changes are associated with changes in the electrostatic potential landscape and interaction mode. These findings advance the understanding of the molecular mechanism underlying the enigmatic salt-induced transitions between different DNA binding site sizes of SSBs. This work demonstrates that monovalent salt is a key regulator of biomolecular interactions that not only play roles in non-specific electrostatic screening effects as usually assumed but also may configure the surface of proteins to contribute to the effective regulation of biomolecular recognition and other downstream events. Cationic and anionic residues on protein surfaces are often inter-connected into hydrogen bond networks to shape protein-ligand interactions. Here it is found that sodium ions not only exhibit electrostatic screen effects but also induce discontinuous structural transition on the protein surface. The transition is instrumental in altering the wrapping of single-stranded DNA on SSB, a key protein in DNA replication, recombination, and repair. image