Conformational Spread in the Flagellar Motor Switch: A Model Study

The reliable response to weak biological signals requires that they be amplified with fidelity. In E. coli, the flagellar motors that control swimming can switch direction in response to very small changes in the concentration of the signaling protein CheY-P, but how this works is not well understood. A recently proposed allosteric model based on cooperative conformational spread in a ring of identical protomers seems promising as it is able to qualitatively reproduce switching, locked state behavior and Hill coefficient values measured for the rotary motor. In this paper we undertook a comprehensive simulation study to analyze the behavior of this model in detail and made predictions on three experimentally observable quantities: switch time distribution, locked state interval distribution, Hill coefficient of the switch response. We parameterized the model using experimental measurements, finding excellent agreement with published data on motor behavior. Analysis of the simulated switching dynamics revealed a mechanism for chemotactic ultrasensitivity, in which cooperativity is indispensable for realizing both coherent switching and effective amplification. These results showed how cells can combine elements of analog and digital control to produce switches that are simultaneously sensitive and reliable. Author Summary: Bacteria swim to find nutrients or to avoid toxins. Their swimming is powered by the rotation of flagella (hair-like structures) that act as propellers. Each flagellum is driven by a rotary molecular engine (the bacterial flagellar motor) that can rotate in either a counterclockwise or clockwise direction and switches between the two directions are frequent and rapid. Although the motor has been studied in detail, we do not understand how it is able to reliably switch direction – a critical function that gives bacteria the ability to steer. In this paper we examined a mathematical model describing how a potential gearbox in the motor might work inside a ring of identical proteins. We compared the output of this model with experimental data on switching speed and other measures of motor function, finding excellent agreement. This is an exciting finding not only because the operation of the motor itself is important, but also because protein complexes play an important and ubiquitous role in cellular signal transduction and therefore, “conformational spread” may be a widespread mechanism for signal propagation in biology.