Suppression of cell-cell variation by cooperative interaction of phosphatase and response regulator.

In bacterial chemotaxis, the output of chemosensing, the concentration of the response regulator CheY-P that was constantly adjusted by the opposing action of the kinase CheA and the phosphatase CheZ, serves as the input of the ultrasensitive flagellar motor that drives bacterial motility. The steady-state kinase activity exhibits large cell-to-cell variation that may result in similar variation in CheY-P concentration. Here, we found that the in vivo phosphatase activity is highly cooperative with respect to CheY-P concentration, and this suppresses the cell-to-cell variation of CheY-P concentration so that it falls within the operational range of the flagellar motor. Therefore, the cooperativity of the CheZ and CheY-P interaction we identified here provided a mechanism of robust coupling between the output of chemosensing and the input of the flagellar motor. Suppression of cell heterogeneity by cooperativity of protein-protein interaction is likely a common feature in many biological signaling systems.