A dynamic-signaling-team model for chemotaxis receptors in Escherichia coli

Abstract

The chemotaxis system of Escherichia coli is sensitive to small relative changes in ambient chemoattractant concentrations over a broad range. Interactions among receptors are crucial to this sensitivity, as is precise adaptation, the return of chemoreceptor activity to prestimulus levels in a constant chemoeffector environment through methylation and demethylation of receptors. Signal integration and cooperativity have been attributed to strongly coupled, mixed teams of receptors, but receptors become individually methylated according to their ligand occupancy states. Here, we present a model of dynamic signaling teams that reconciles strong coupling among receptors with receptor-specific methylation. Receptor trimers of dimers couple to form a honeycomb lattice, consistent with cryo-electron microscopy (cryoEM) tomography, within which the boundaries of signaling teams change rapidly. Our model helps explain the inferred increase in signaling team size with receptor modification, and indicates that active trimers couple more strongly than inactive trimers.adaptation | modeling | receptor clustering A daptation to persistent stimuli is important in maintaining a broad range of response-sensitivity in numerous sensory systems, including visual (1), olfactory (2), and auditory (3). The best understood example of such adaptation is the Escherichia coli chemotaxis system (Fig. 1A), in which receptor signaling adapts precisely to persistent chemoeffector concentrations. Adaptation is implemented by the methylation and demethylation of transmembrane receptors through an integral-feedback control mechanism (4, 5). Different receptor types bind specific ligands, but signal cooperatively in mixed teams (6, 7). One feature of this system that has remained mysterious is that, at short times, adaptation leads to similar modification of all receptors, but at longer times, modification is receptor-type specific, affecting primarily the receptors stimulated by ligand (8). Here, we present a model of dynamic-signaling teams that reconciles receptor cooperativity with receptor-specific methylation.Receptors direct cell movement by biasing the switching between tumbling and straight-swimming states, producing a biased random walk up gradients of chemoattractants or down gradients of chemorepellents. Of the five receptor types in E. coli, the highest abundance are Tar (aspartate binding) and Tsr (serine binding). Receptors form homodimers that can each bind one molecule of ligand. Homodimers, which we will refer to as receptors, in turn form mixed trimers of dimers, and associate with the linker protein CheW and the histidine kinase CheA (9). Receptor signaling activates CheA autophosphorylation, and the phosphoryl group is transferred to the response regulator CheY (or to the methylesterase CheB). Phosphorylated CheY diffuses and binds to the flagellar motors, causing tumbling. CheY is dephosphorylated by the phosphatase CheZ. Receptor trimers of dimers form the basic signaling units, with single receptors unable to activate Che...

The source of high signal cooperativity in bacterial chemosensory arrays

“…7 summarizes our present findings in the context of other recent work on the E. coli chemosensory array. Our results demonstrate, as proposed in current array models, that interface 2 interactions between CheW and the P5 domain of CheA link individual receptor core complexes into larger structural and allosteric signaling units that have been designated receptor teams (30)(31)(32)(33). Mutant CheA or CheW proteins with interface 2 defects assembled signaling complexes that both activated CheA autophosphorylation and inhibited that activity in response to attractant ligands; however, when coupled to receptors with uniform adaptational modification states, the kinase control responses of interface 2 mutants exhibited little or no cooperativity (Hill coefficients <2), in contrast to those of their wild type counterparts (Hill coefficients >15).…”

“…The chemosensory array comprises numerous receptor teams, whose sizes and network connections change in response to signal state transitions elicited by chemoeffector stimuli (25,27) and by adaptational modifications (32,33). The kinase-ON state promotes assembly of core complexes into receptor teams, whereas the kinase-OFF state promotes disassembly of receptor teams.…”

Chemotactic adaptation kinetics of individual Escherichia coli cells

“…In particular, we quantified two features of adaptation: (i) abruptness (the degree to which return to prestimulus behavior occurs within a small number of run/tumble events) and (ii) overshoot (the degree of excessive response before the return to prestimulus behavior). Though abruptness and overshoot have been previously reported in the literature (9,16,(21)(22)(23), they have not yet been characterized in detail. Here, we quantify both features in response to both step-up and step-down stimuli across a broad range of stimulus strengths.…”

Universal Response-Adaptation Relation in Bacterial Chemotaxis

“…Instead, our results confirm theoretical predictions that the RA alignment for different ligands is ensured by the allosteric interactions of receptors within the sensory clusters. Such interactions are predicted to couple not only the activities of different receptors but also their methylation kinetics (51,53), because the binding of an attractant molecule to any of the receptors in the allosteric signaling team reduces the activity of the entire team and therefore initially stimulates increased methylation of all receptors. Although due to the incomplete coupling between receptors such cross-methylation is only transient (51,56), it is apparently sufficient to align the adaptation rates for different ligands in the case of the subsaturating stimulation in our experiments.…”

“…Instead, the alignment of the RA relation for different ligands can be easily explained by the Monod-Wyman-Changeux (MWC) model of allosteric interactions between different receptors in sensory complexes (12,14,16,51,53). Because these interactions couple the activity states of different receptors, the inactivation of one receptor by its ligand leads to the inactivation of other receptors in the same complex.…”