Functional Determinants of a Small Protein Controlling a Broadly Conserved Bacterial Sensor Kinase

Abstract

One of the primary means by which bacteria adapt to their environment is through pairs of proteins consisting of a sensor and a response regulator. A small membrane protein, MgrB, impedes the activity of sensor protein PhoQ, thereby affecting the expression of PhoQ regulated virulence genes in pathogenic bacteria. However, it is unknown how such a small protein modulates the activity of PhoQ. Here, we studied the functional determinants of MgrB and identified specific amino acids critical for the protein's inhibitory function. Notably, we find that the membrane-spanning region is important for MgrB interaction with PhoQ. Additionally, this region appears to physically interact with other sensors, a property that may be important for evolving small protein regulators of sensor kinases.