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      Quantitative modeling of sensitivity in bacterial chemotaxis: The role of coupling among different chemoreceptor species

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      Proceedings of the National Academy of Sciences
      Proceedings of the National Academy of Sciences

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          Abstract

          We propose a general theoretical framework for modeling receptor sensitivity in bacterial chemotaxis, taking into account receptor interactions, including those among different receptor species. We show that our model can quantitatively explain the recent in vivo measurements of receptor sensitivity at different ligand concentrations for both mutant and wild-type strains. For mutant strains, our model can fit the experimental data exactly. For the wild-type cell, our model is capable of achieving high gain while having modest values of Hill coefficient for the response curves. Furthermore, the high sensitivity of the wild-type cell in our model is maintained for a wide range of ambient ligand concentrations, facilitated by near-perfect adaptation and dependence of ligand binding on receptor activity. Our study reveals the importance of coupling among different chemoreceptor species, in particular strong interactions between the aspartate (Tar) and serine (Tsr) receptors, which is crucial in explaining both the mutant and wild-type data. Predictions for the sensitivity of other mutant strains and possible improvements of our model for the wild-type cell are also discussed.

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          Most cited references20

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          Robustness in simple biochemical networks.

          Cells use complex networks of interacting molecular components to transfer and process information. These "computational devices of living cells" are responsible for many important cellular processes, including cell-cycle regulation and signal transduction. Here we address the issue of the sensitivity of the networks to variations in their biochemical parameters. We propose a mechanism for robust adaptation in simple signal transduction networks. We show that this mechanism applies in particular to bacterial chemotaxis. This is demonstrated within a quantitative model which explains, in a unified way, many aspects of chemotaxis, including proper responses to chemical gradients. The adaptation property is a consequence of the network's connectivity and does not require the 'fine-tuning' of parameters. We argue that the key properties of biochemical networks should be robust in order to ensure their proper functioning.
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            An ultrasensitive bacterial motor revealed by monitoring signaling proteins in single cells.

            Understanding biology at the single-cell level requires simultaneous measurements of biochemical parameters and behavioral characteristics in individual cells. Here, the output of individual flagellar motors in Escherichia coli was measured as a function of the intracellular concentration of the chemotactic signaling protein. The concentration of this molecule, fused to green fluorescent protein, was monitored with fluorescence correlation spectroscopy. Motors from different bacteria exhibited an identical steep input-output relation, suggesting that they actively contribute to signal amplification in chemotaxis. This experimental approach can be extended to quantitative in vivo studies of other biochemical networks.
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              Receptor sensitivity in bacterial chemotaxis.

              Chemoreceptors in Escherichia coli are coupled to the flagella by a labile phosphorylated intermediate, CheY approximately P. Its activity can be inferred from the rotational bias of flagellar motors, but motor response is stochastic and limited to a narrow physiological range. Here we use fluorescence resonance energy transfer to monitor interactions of CheY approximately P with its phosphatase, CheZ, that reveal changes in the activity of the receptor kinase, CheA, resulting from the addition of attractants or repellents. Analyses of cheR and/or cheB mutants, defective in receptor methylation/demethylation, show that response sensitivity depends on the activity of CheB and the level of receptor modification. In cheRcheB mutants, the concentration of attractant that generates a half-maximal response is equal to the dissociation constant of the receptor. In wild-type cells, it is 35 times smaller. This amplification, together with the ultrasensitivity of the flagellar motor, explains previous observations of high chemotactic gain.
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                Author and article information

                Journal
                Proceedings of the National Academy of Sciences
                PNAS
                Proceedings of the National Academy of Sciences
                0027-8424
                1091-6490
                July 08 2003
                July 08 2003
                July 08 2003
                June 25 2003
                : 100
                : 14
                : 8223-8228
                Article
                10.1073/pnas.1330839100
                166210
                12826616
                15893a0b-dfe0-4f4a-b44f-c6592bb086b2
                © 2003
                History

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