Effects of adaptation in maintaining high sensitivity over a wide range of backgrounds for Escherichia coli chemotaxis.
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.
Mello
Bernardo A
BA
IBM T. J. Watson Research Center, Yorktown Heights, New York, USA.
Tu
Yuhai
Y
D000222:Adaptation, Physiological / Q000187:drug effects / Q000502:physiology*; D001224:Aspartic Acid / Q000008:administration & dosage*; D001426:Bacterial Proteins; D002628:Chemoreceptor Cells / Q000187:drug effects / Q000502:physiology*; D002630:Chemotactic Factors / Q000008:administration & dosage; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology*; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000187:drug effects / Q000502:physiology*; D008954:Models, Biological; D012680:Sensitivity and Specificity
D001426:Bacterial Proteins; D002630:Chemotactic Factors; D001224:Aspartic Acid