Functional Determinants of a Small Protein Controlling a Broadly Conserved Bacterial Sensor Kinase
Srujana S. Yadavalli, Ted Goh, Jeffrey N. Carey, Gabriele Malengo, Sangeevan Vellappan, Bryce E. Nickels, Victor Sourjik, Mark Goulian, Jing Yuan
Abstract
we find that the MgrB TM region is necessary for PhoQ inhibition. Our results indicate that the TM region mediates interactions with PhoQ and that W20 is a key residue for PhoQ/MgrB complex formation. Additionally, mutations of the MgrB cytosolic region suggest that the two N-terminal lysines play an important role in regulating PhoQ activity. Alanine scanning mutagenesis of the periplasmic region of MgrB further indicates that, with the exception of a few highly conserved residues, most residues are not essential for MgrB's function as a PhoQ inhibitor. Our results indicate that the regulatory function of the small protein MgrB depends on distinct contributions from multiple residues spread across the protein. Interestingly, the TM region also appears to interact with other non-cognate histidine kinases in a bacterial two-hybrid assay, suggesting a potential route for evolving new small protein modulators of histidine kinases.