Chemosensing in Escherichia coli : Two regimes of two-state receptors

Abstract

The chemotaxis network in Escherichia coli is remarkable for its sensitivity to small relative changes in the concentrations of multiple chemical signals. We present a model for signal integration by mixed clusters of interacting two-state chemoreceptors. Our model results compare favorably to the results obtained by Sourjik and Berg with in vivo fluorescence resonance energy transfer. Importantly, we identify two distinct regimes of behavior, depending on the relative energies of the two states of the receptors. In regime I, coupling of receptors leads to high sensitivity, while in regime II, coupling of receptors leads to high cooperativity, i.e., high Hill coefficient. For homogeneous receptors, we predict an observable transition between regime I and regime II with increasing receptor methylation or amidation.chemotaxis ͉ Monod, Wyman, and Changeux model ͉ receptor clustering T he chemotaxis network in Escherichia coli is the best studied signal-transduction network of any living organism. The function of the network is to allow E. coli to swim toward attractants, such as amino acids or sugars, and away from repellents. The cells perform chemotaxis by detecting temporal changes in their chemical environment and transducing this information into a decision to swim straight or change direction (tumble). The chemotaxis system is remarkable for its high sensitivity to small relative changes in chemical concentrations and for the ability of cells to retain sensitivity over a wide range of ambient chemoeffector levels (1). The latter property relies on an adaptation system in which receptors are methylated͞ demethylated by CheR͞CheB at four specific residues (modification sites) (2, 3). Adaptation in chemotaxis is precise, i.e., cells return precisely to the same rate of tumbles if chemoeffector levels stop changing. The adaptation system is also robust in that precise adaptation occurs for a range of levels of chemotaxis proteins (4). Another remarkable property of the system is its ability to integrate signals from different chemical cues, allowing chemotaxis toward any of multiple attractants (5).In E. coli, there are five chemotaxis receptors: two highabundance receptors, Tar and Tsr, and three low-abundance receptors Tap, Trg, and Aer. These receptors are highly similar in their cytoplasmic signaling domains, with differences primarily in the periplasmic ligand-binding domains. All five chemoreceptors associate as homodimers. In living cells, these homodimers are observed to cluster near one or both poles of the cell (6). In vitro crystallographic studies of cytoplasmic domains of the receptors reveal a complex of three homodimers (a ''trimer of dimers'') (7). In vivo crosslinking studies demonstrate that trimers of dimers can be composed of mixtures of homodimers of different types (8, 9). Clustering of trimers of dimers is mediated by the linker protein CheW and by the kinase CheA (6, 8), both of which are essential for phosphorylation of the response regulator CheY (10). In its phosphorylated form, CheY in...

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Fast, high-throughput measurement of collective behaviour in a bacterial population

“…This is currently explained through the cooperativity of the receptors, which react in clusters of dimers to the binding of a ligand [20][21][22][23], and of the molecules in the ring controlling the flagellar motor rotation [24,25], which can cooperatively rearrange to induce a motor switch in response to a single CheY binding event. The response is also subject to adaptation: the MCPs are desensitized by successive methylations (governed by the proteins CheR and CheB) [17], so that the activity of CheA, and hence the tumbling rate, finally adapts to a new background concentration of the chemoattractant.…”