The structure of <i>Streptococcus gordonii</i> surface protein SspB in complex with TEV peptide provides clues to oral streptococcal adherence to salivary agglutinin

<i>Streptococcus gordonii</i> is a commensal bacterium in the oral cavity and has many surface adhesins that have been well characterized. SspA/B belongs to the Antigen I/II-like family of proteins, which are well known for their multifunctional adherence capabilities. Most AgI/II-like proteins adhere to salivary agglutinin (also known as glycoprotein 340, Gp340). In an effort to identify the putative binding site on the AgI/II-like family of proteins, we conducted structural studies to determine the V-domain of SspB. In this paper, we report the structure of SspB's V-domain in complex with a TEV-peptide that was inserted to cleave the histidine tag at the C-terminus after purification. This peptide shared sequence and structural homology with a helical region on the scavenger receptor cysteine-rich (SRCR) domain of Gp340. Our studies with the synthetic peptide PepCD1^SRCR show that it inhibits the <i>Streptococcus mutans</i> biofilm formation in a dose-dependent manner. A comprehensive comparative analysis of this site with the corresponding sites in the homologous V-domains of <i>S. mutans</i> AgI/II and GbpC established that most of these interface residues were conserved. Based on the structural data, mutational analysis was initiated to study the effect of binding-interface residues on the ability of each of these V-domains from <i>S. mutans</i> and <i>S. gordonii</i> to adhere to salivary agglutinin. Here, we report for the first time the binding site for the V-regions that are distinct among oral streptococci, which provides potential opportunities for therapeutic intervention of pathogenic species.