Signal amplification in a lattice of coupled protein kinases.
The bacterium Escherichia coli detects chemical attractants and repellents by means of a cluster of transmembrane receptors and associated molecules. Experiments have shown that this cluster amplifies the signal about 35-fold and current models attribute this amplification to cooperative interactions between neighbouring receptors. However, when applied to the mixed population of receptors of wild-type E. coli, these models lead to indiscriminate methylation of all receptor types rather than the selective methylation observed experimentally. In this paper, we propose that cooperative interactions occur not between receptors but in the underlying lattice of CheA molecules. In our model, each CheA molecule is stimulated by its neighbours via their flexible P1 domains and modulated by the ligand binding and methylation states of associated receptors. We test this idea with detailed, molecular-based stochastic simulations and show that it gives an accurate reproduction of signalling in this system, including ligand-specific adaptation.
Goldman
Jacki P
JP
Department of Physiology, Development, and Neuroscience, University of Cambridge, UK.
Levin
Matthew D
MD
Bray
Dennis
D
D001224:Aspartic Acid / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism*; D002630:Chemotactic Factors / Q000378:metabolism; D002633:Chemotaxis; D003198:Computer Simulation; D004926:Escherichia coli / Q000201:enzymology / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000378:metabolism*; D000071677:Histidine Kinase; D008565:Membrane Proteins / Q000378:metabolism*; D000072236:Methyl-Accepting Chemotaxis Proteins; D008745:Methylation; D008954:Models, Biological; D011494:Protein Kinases / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015398:Signal Transduction; D013269:Stochastic Processes
D001426:Bacterial Proteins; D002630:Chemotactic Factors; D029968:Escherichia coli Proteins; D008565:Membrane Proteins; D000072236:Methyl-Accepting Chemotaxis Proteins; D011956:Receptors, Cell Surface; D001224:Aspartic Acid; D011494:Protein Kinases; D000071677:Histidine Kinase; C000607608:cheA protein, E coli