Tightly Regulated, yet Flexible and Ultrasensitive, 2 Directional Switching Mechanism of a Rotary Motor

Biological switches are wide spread in many biological systems. Among them, the switch of the bacterial flagellar motor has been, for years, a focus of special interest. This is because it affects a mechanical process rather than a chemical reaction, it controls the direction of rotation of a rotary motor rather than being an on/off switch, and it is exceptionally ultrasensitive. Yet, the molecular mechanism underlying the function of this switch has remained unknown. Here we resolved unique features of this mechanism: On the one hand, it is tightly regulated by multiple means, involving three binding sites and two different covalent modifications, with the binding specificity being dictated by the type of covalent modification and by a strict binding sequence. On the other hand, it endows the motor with flexibility as it involves an intermediate stage of brief switches that provides a “go/no go” situation, in which the motor can either proceed to a stable rotation in the new direction or shift back to the original direction. This intermediate stage appears to be a means of a swimming cell to produce angular deflection while maintaining directional persistence. Furthermore, we show by mathematical modeling that such a mechanism provides ultrasensitivity. This unique combination of tight regulation, flexibility, and ultrasensitivity make this mechanism of special interest.