Exploring the function of novel arginine phosphorylation in streptococcal physiology

ABSTRACT
Post-translational modification (PTM) by phosphorylation plays an important role in protein folding, stability, and
function. In bacteria, protein phosphorylation plays a key role in bacterial physiology and virulence gene
regulation (pathogenesis) by participating in signal sensing and transduction networks. Protein phosphorylation
occurs predominantly on six amino acids, and they form different chemical bonds. Phosphorylation of serine,
threonine, and tyrosine residues forms a stable ester bond. Phosphorylation of aspartate and histidine forms a
relatively unstable phosphoramidate P-N bond. These two types of phosphorylation are predominantly involved
in signal transduction and gene regulation. On the other hand, phosphorylation of the arginine residue (Arg) is a
novel mode of PTM recently discovered in Bacillus subtilis, Staphylococcus aureus, and Mycolibacterium
smegmatis. In these organisms, Arg phosphorylation occurs in >100 different proteins and is involved in protein
quality control, translational, and transcriptional regulations. Despite the importance in the bacterial physiology,
nothing is known about Arg phosphorylation in Streptococcus, a medically important genus. We found that in
Streptococcus mutans, a dental pathogen, Arg-phosphorylation occurs; however, the homolog of the B. subtilis
and S. aureus Arg-kinase (McsB) is conspicuously absent in streptococci. The major goals of this study are to
understand the physiological role of Arg-phosphorylation in S. mutans and to identify the putative kinase enzyme
responsible for Arg-phosphorylation in streptococci.

Grant Number: 5R21DE033883-02
NIH Institute/Center: NIH
Principal Investigator: Indranil Biswas