Characterization of Multi-Domain Proteins in the ArsR/SmtB Family of Transcriptional Regulators

Studies centered on single-domain proteins revealed several fundamental characteristics about how they work, but the multimeric proteins are more complex. Analysis of multimeric protein sequences and their three-dimensional structures revealed several important characteristics about these proteins, still, further analyses are required especially in the context of how multi-domain proteins evolved from the single domain ones. In the present study, we have created a dataset of the ArsR/SmtB family of proteins to study how multimeric proteins in the family evolved from the single-domain ones. The ArsR/SmtB family is one of the diverse groups of prokaryotic proteins which primarily function as transcriptional regulators. These proteins generally regulate metal-efflux pumps that pump out the toxic metal ions from the cell when intracellular concentrations of metal ions rise at alarming levels. We have found that in ArsR/SmtB family, protein sequences having more than 150 aa tend to lose their metal-binding residues located in the ArsR domain and additional domains start to appear which may take dominant roles in the overall functionality of the protein. Based on our analysis we proposed a model on how multi-domain proteins may have evolved from single-domain proteins in the ArsR/SmtB family.