Effects of Adaptation in Maintaining High Sensitivity over a Wide Range of Backgrounds for Escherichia coli Chemotaxis

Abstract

An allosteric model is developed to study the cooperative kinase response of wild-type (wt) Escherichia coli cells to the chemoattractant MeAsp in different ambient MeAsp concentrations. The model, together with wt dose response data, reveals the underlying mechanism for E. coli's ability to maintain high sensitivity over a wide range of backgrounds. We find: 1), Adaptation tunes the system to the steepest part of the dose response curve, where the sensitivity to a given type of stimulus is amplified by the number of corresponding receptors in the (mixed) functional receptor complex. A lower bound on the number of Tar receptor dimers (Na) in the complex Na>approximately 6 is obtained from the measured sensitivity. 2), Accurate adaptation synchronizes the kinase activities from different (uncoupled) receptor complexes in a single cell and is crucial in maintaining the high Hill coefficient in the (population averaged) kinase response curve. 3), The wide dynamic range of the high sensitivity can be explained in our model by either having a very small ratio between ligand dissociation constants of the inactive and the active receptors C=0.006, Na=6, and a (methylation level independent) dissociation constant for the inactive Tar receptor K=18.2 microM or by having K and/or Na increase with receptor methylation level together with a larger value of C>0.01. Specific experiments are suggested to distinguish these two scenarios. 4), The receptor occupancy in a wt cell should also adapt and exhibit a slow (approximately logarithmic) dependence on the ligand concentration in the adapted state; this general prediction can be tested experimentally to verify/falsify our model.

Chemoreceptors in Caulobacter crescentus : Trimers of Receptor Dimers in a Partially Ordered Hexagonally Packed Array

“…Thus, our studies demonstrate that within the context of an approximate hexagonal lattice, chemoreceptors display local disorder. Quantitative models, based primarily on experimental response measurements derived from E. coli cells, describe the high-performance features of bacterial chemotaxis and predict that chemoreceptors form allosteric arrays with as many as several dozen signaling units acting cooperatively via clustered neighborhoods of strongly coupled receptors (9,11,12,17). The model we present here for native Caulobacter chemoreceptor arrays confirms this expectation and demonstrates how chemoreceptors can achieve local clustering while positioned in the context of a partially ordered, hexagonally packed lattice (Fig.…”

Allosteric proteins as logarithmic sensors

“…Tu and coworkers analyzed a dynamic version of the model in the context of bacterial chemotaxis (19,22) by taking partial derivatives with respect to c,…”

Bacterial chemoreceptors: high-performance signaling in networked arrays

“…Qualitatively, a two-state model explains the major features of the chemotaxis system, but quantitative and modeling studies indicate that additional complexity is present that extends the dynamic range of the system beyond that possible for a simple two-state model [13,17,61].…”

“…The 'kinase-on' conformation has low attractant affinity, low methylation propensity and high demethylation propensity. Because rates of modification are slow on the time-scale of binding an attractant or a repellent, the extent of receptor methylation provides a record of the recent chemical past with which to make comparisons to current chemoeffector levels, reflected in the extent of receptor ligand occupancy.Qualitatively, a two-state model explains the major features of the chemotaxis system, but quantitative and modeling studies indicate that additional complexity is present that extends the dynamic range of the system beyond that possible for a simple two-state model [13,17,61]. …”