The W-Acidic Motif of Histidine Kinase WalK Is Required for Signaling and Transcriptional Regulation in Streptococcus mutans

In Streptococcus mutans, we find that the histidine kinase Walk possesses the longest C-terminal tail (CTT) among all 14 TCSs, and this tail plays a key role in the interaction of WalK with its response regulator WaIR. We demonstrate that the intrinsically disordered CTT is characterized by a conserved tryptophan residue surrounded by acidic amino acids. Mutation in the tryptophan not only disrupts the stable interaction, but also impairs the efficient phosphotransferase and phosphatase activities of WaIRK. In addition, the tryptophan is important for WalK to compete with DNA containing a WaIR binding motif for the WaIR interaction. We further show that the tryptophan is important for in vivo transcriptional regulation and bacterial biofilm formation by S. mutans. Moreover, Staphylococcus aureus Walk also has a characteristic CTT, albeit relatively shorter, with a conserved W-acidic motif, that is required for the WaIRK interaction in vitro. Together, these data reveal that the W-acidic motif of Walk is indispensable for its interaction with WaIR, thereby playing a key role in the WaIRK-dependent signal transduction, transcriptional regulation and biofilm formation.

Automated summary

In Streptococcus mutans, the histidine kinase Walk's long C-terminal tail is crucial for its interaction with the response regulator WaIR, and plays a key role in signal transduction, transcriptional regulation, and biofilm formation.