A predictive computational model of the kinetic mechanism of stimulus-induced transducer methylation and feedback regulation through CheY in archaeal phototaxis and chemotaxis

By mathematical modeling we infer the kinetic mechanisms of stimulus-induced transducer methylation and adaptation. The model (deterministic and in the form of ordinary differential equations) correctly predicts experimentally observed transducer demethylation (as detected by released methanol) in response to attractant and repellent stimuli of wildtype cells, a cheY deletion mutant, and a mutant in which the stimulated transducer species is methylation-deficient.We provide a kinetic model for signal processing in photo- and chemotaxis in the archaeon H. salinarum suggesting an essential role of receptor cooperativity, antagonistic reversible methylation, and a CheY-dependent feedback on transducer demethylation.The archaeon Halobacterium salinarum swims by rotation of a semi-rigid right-handed flagellar bundle [1]. Each flagellar filament of the bundle extends the axis of a rotary motor to passively transduce the mechanical energy generated by the motor to the medium. Motors are anchored in the cell membrane and driven by ATP [2]. Cells swim back and forth by switching the sense of flagellar rotation from clockwise to counterclockwise and vice versa [1,3]. In adapted or unstimulated cells, switching occurs spontaneously. Active swimming and motor switching is superimposed with passive Brownian motion of cell body and flagellar bundle [4]. By the resulting random swimming paths, the cells explore their environment until they encounter a stimulus. Sensory stimulation of the photo- or chemoreceptors transiently modulates the probability of motor switching, resulting in a movement of the cell towards more favorable regions in the environment [5,6]. Rather than sensing absolute stimulus strengths, cells respond to relative changes by adapting to any stimulus of constant intensity [7,8].Several lines of evidence suggest that in bacteria as well as in archaea this adaptation is at least partially caused by reversible methylation of methyl-accepting taxis proteins [7,9,10]