Gain Paradox

Part of the Biological and Medical Physics, Biomedical Engineering book series (BIOMEDICAL)


Data obtained early on suggested that the chemotactic response is proportional to the change in receptor occupancy, with that occupancy characterized by a fixed dissociation constant, K d, the concentration of ligand at which the probability of receptor occupancy is 1/2 (Berg and Tedesco, 1975; Mesibov et al., 1973). Then it became evident that the dissociation constant increases (i.e., cells become less sensitive) at higher concentrations of ligand, as receptors are methylated (Borkovich et al., 1992; Bornhorst and Falke, 2000; Dunten and Koshland 1991; Li and Weis, 2000). However, even at these higher concentrations (e.g., for the nonmetabolizable aspartate analog α-methylaspartate at an ambient concentration of 0.16 mM) the gain is prodigious: a step increase in concentration from 0.16 to 0.16 + 0.0027 mM (a change of about 1.7%) transiently increases the probability that the motor spins counterclockwise (CCW) by 0.23 (Segall et al., 1986). Computer simulations of the chemotaxis system (e.g., Bray et al., 1993; reviewed by Bray, 2002) fail to predict the necessary gain. Two recent findings appear to resolve the paradox. First, there is an amplification step at the beginning of the signaling pathway: the fractional change in kinase activity is some 35 times larger than the fractional change in receptor occupancy (Sourjik and Berg, 2002a).


Receptor Occupancy Ambient Concentration Fractional Change Chemotactic Response Receptor Cluster 
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  1. Alon, U., M. G. Surette, N. Barkai, and S. Leibler. 1999. Robustness in bacterial chemotaxis. Nature 397:168–171.CrossRefADSGoogle Scholar
  2. Ames, P., C. A. Studdert, R. H. Reiser, and J. S. Parkinson. 2002. Collaborative signaling by mixed chemoreceptor teams in Escherichia coli. Proc. Natl. Acad. Sci. USA 99:7060–7065.CrossRefADSGoogle Scholar
  3. Barkai, N., and S. Leibler. 1997. Robustness in simple biochemical networks. Nature 387:913–917.CrossRefADSGoogle Scholar
  4. Berg, H. C., and E. M. Purcell. 1977. Physics of chemoreception. Biophys. J. 20:193–219.ADSCrossRefGoogle Scholar
  5. Berg, H. C., and P. M. Tedesco. 1975. Transient response to chemotactic stimuli in Escherichia coli. Proc. Natl. Acad. Sci. USA 72:3235–3239.CrossRefADSGoogle Scholar
  6. Berg, H. C., and L. Turner. 1995. Cells of Escherichia coli swim either end forward. Proc. Natl. Acad. Sci. USA 92:477–479.CrossRefADSGoogle Scholar
  7. Borkovich, K. A., L. A. Alex, and M. I. Simon. 1992. Attenuation of sensory receptor signaling by covalent modification. Proc. Natl. Acad. Sci. USA 89:6756–6760.CrossRefADSGoogle Scholar
  8. Bornhorst, J. A., and J. J. Falke. 2000. Attractant regulation of the aspartate receptor-kinase complex: limited cooperative interactions between receptors and effects of the receptor modification state. Biochemistry 39:9486–9493.CrossRefGoogle Scholar
  9. Bray, D. 2002. Bacterial chemotaxis and the question of gain. Proc. Natl. Acad. Sci. USA 99:7–9.Google Scholar
  10. Bray, D., R. B. Bourret, and M. I. Simon. 1993. Computer simulation of the phosphorylation cascade controlling bacterial chemotaxis. Mol. Biol. Cell 4:469–482.Google Scholar
  11. Cluzel, P., M. Surette, and S. Leibler. 2000. An ultrasensitive bacterial motor revealed by monitoring signaling proteins in single cells. Science 287:1652–1655.CrossRefADSGoogle Scholar
  12. Duke, T. A. J., and D. Bray. 1999. Heightened sensitivity of a lattice of membrane receptors. Proc. Natl. Acad. Sci. USA 96:10104–10108.CrossRefADSGoogle Scholar
  13. Duke, T. A. J., N. Le Novère, and D. Bray. 2001. Conformational spread in a ring of proteins: a stochastic approach to allostery. J. Mol. Biol. 308:541–553.CrossRefGoogle Scholar
  14. Dunten, P., and D. E. Koshland, Jr. 1991. Tuning the responsiveness of a sensory receptor via covalent modification. J. Biol. Chem. 266: 1491–1496.Google Scholar
  15. Falke, J. L. 2002. Cooperactivity between bacterial chemotaxis receptors. Proc. Natl. Acad. Sci. USA 99:6530–6532.CrossRefADSGoogle Scholar
  16. Gestwicki, J. E., and L. L. Kiessling. 2002. Inter-receptor communication through arrays of bacterial chemoreceptors. Nature 415:81–84.CrossRefADSGoogle Scholar
  17. Li, G., and R. M. Weis. 2000. Covalent modification regulates ligand binding to receptor complexes in the chemosensory system of Escherichia coli. Cell 100:357–365.CrossRefGoogle Scholar
  18. Maddock, J. R., and L. Shapiro. 1993. Polar location of the chemoreceptor complex in the Escherichia coli cell. Science 259:1717–1723.CrossRefADSGoogle Scholar
  19. Mesibov, R., G. W. Ordal, and J. Adler. 1973. The range of attractant concentrations for bacterial chemotaxis and the threshold and size of response over this range. J. Gen. Physiol. 62:203–223.CrossRefGoogle Scholar
  20. Monod, J., J. Wyman, and J.-P. Changeux. 1965. On the nature of allosteric transitions: a plausible model. J. Mol. Biol. 12:88–118.CrossRefGoogle Scholar
  21. Segall, J. E., S. M. Block, and H. C. Berg. 1986. Temporal comparisons in bacterial chemotaxis. Proc. Natl. Acad. Sci. USA 83:8987–8991.CrossRefADSGoogle Scholar
  22. Shimizu, T. S., N. Le Novère, M. D. Levin, A. J. Beavil, B. J. Sutton, and D. Bray. 2000. Molecular model of a lattice of signalling proteins involved in bacterial chemotaxis. Nature Cell Biol. 2:1–5.CrossRefGoogle Scholar
  23. Sourjik, V., and H. C. Berg. 2000. Localization of components of the chemotaxis machinery of Escherichia coli using fluorescent protein fusions. Mol. Microbiol. 37:740–751.CrossRefGoogle Scholar
  24. Sourjik, V., and H. C. Berg. 2002a. Receptor sensitivity in bacterial chemotaxis. Proc. Natl. Acad. Sci. USA 99:123–127.CrossRefADSGoogle Scholar
  25. Sourjik, V., and H. C. Berg. 2002b. Binding of the Escherichia coli response regulator CheY to its target measured in vivo by fluorescence resonance energy transfer. Proc. Natl. Acad. Sci. USA 99:12669–12674.CrossRefADSGoogle Scholar

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© Springer-Verlag New York, Inc. 2004

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