The essential tension: opposed reactions in bacterial two-component regulatory systems

Russo, Frank D.; Silhavy, Thomas J.

doi:10.1016/0966-842x(93)90007-e

Cited by 115 publications

(106 citation statements)

References 26 publications

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“…These equations reduce to a cubic equation for [OmpR-P], the solution of which is a complicated function of all 10 parameters, including in particular [EnvZ] T . We thus find that in this model, in contrast to a model in which the phosphorylation and dephosphorylation activities of EnvZ function independently (13,15), the output of the circuit ([OmpR-P]) depends on the total amount of EnvZ. The EnvZ͞OmpR circuit in E. coli, however, has an interesting operating point: the amount of EnvZ in the cell is much less than the amount of OmpR (37, 38).…”

Section: A Model Of the Envz͞ompr Circuit Predicts Robust Outputmentioning

confidence: 75%

“…Within the context of the EnvZ͞OmpR two-component system it has been argued on the basis of a simplified model that the bifunctional nature of EnvZ results in a circuit output (the concentration of OmpR-P) that is insensitive to variations in the total concentrations of EnvZ ([EnvZ] T ) and OmpR ([OmpR] T ) (13,15). The central assumptions of this model, however, are in conflict with more recent work in which the regions within EnvZ responsible for the autokinase, phosphotransfer, and phosphatase activities were shown to overlap and interact (25)(26)(27)(28)(29).…”

Section: Discussionmentioning

confidence: 99%

“…Previously, it was suggested on the basis of a simplified model for the EnvZ-mediated cycle of phosphorylation and dephosphorylation of OmpR that the output of the circuit (the concentration of OmpR-P) should be independent of the total concentration of EnvZ and OmpR in the cell (13,15). The notion that the complex networks of interacting molecules within cells should be robust (i.e., insensitive) to variations in many of the parameters that characterize the constituent reactions has appeared in various contexts in cell biology (e.g., refs.…”

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confidence: 99%

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Robustness and the cycle of phosphorylation and dephosphorylation in a two-component regulatory system

Batchelor

Goulian

2003

Proc. Natl. Acad. Sci. U.S.A.

227

308

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The EnvZ͞OmpR system in Escherichia coli, which regulates the expression of the porins OmpF and OmpC, is one of the simplest and best-characterized examples of two-component signaling. Like many other histidine kinases, EnvZ is bifunctional; it phosphorylates and dephosphorylates the response regulator OmpR. We have analyzed a mathematical model of the EnvZ-mediated cycle of OmpR phosphorylation and dephosphorylation. The model predicts that when EnvZ is much less abundant than OmpR, as is the case in E. coli, the steady-state level of phosphorylated OmpR (OmpR-P) is insensitive to variations in the concentration of EnvZ. The model also predicts that the level of OmpR-P is insensitive to variations in the concentration of OmpR when the OmpR concentration is sufficiently high. To test these predictions, we have perturbed the porin regulatory circuit in E. coli by varying the expression levels of EnvZ and OmpR. We have constructed two-color fluorescent reporter strains in which ompF and ompC transcription can be easily measured in the same culture. Using these strains we have shown that, consistent with the predictions of our model, the transcription of ompC and ompF is indeed robust or insensitive to a wide range of expression levels of both EnvZ and OmpR.A mong prokaryotes, a remarkable number of cellular functions are controlled by two-component regulatory systems. Dedicated circuits transduce and interpret specific signals such as pH, temperature, osmolarity, light, nutrients, ions, pheromones, and toxins to regulate a wide range of processes including motility, virulence, metabolism, the cell cycle, developmental switches, antibiotic resistance, and stress responses (for reviews see for example refs. 1-4). Most of the detailed features of these circuits are quite varied and depend on the particular signals that are detected and the responses that are effected. However, all twocomponent systems transmit information via phosphorylation of a histidine on one protein (a histidine kinase) followed by transfer of phosphate to an aspartic acid, which is usually on a distinct protein (a response regulator). A notable feature of many of these systems is that the histidine kinase is bifunctional: it phosphorylates and dephosphorylates its cognate response regulator. This feature raises the interesting question of what is gained by implementing a regulatory circuit in this manner. Would a circuit in which, for example, phosphorylation is controlled by the histidine kinase and dephosphorylation is caused by spontaneous hydrolysis or a separate phosphatase have important differences from a circuit in which both reactions are mediated by the same enzyme?A particularly well-characterized example of a bifunctional histidine kinase is EnvZ. In Escherichia coli, EnvZ responds to changes in the extracellular osmolarity of inner-membrane impermeable compounds and controls the phosphorylation of the response regulator OmpR. OmpR, in turn, regulates the transcription of a number of genes, the best characterized of which are ompF a...

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Section: A Model Of the Envz͞ompr Circuit Predicts Robust Outputmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Robustness and the cycle of phosphorylation and dephosphorylation in a two-component regulatory system

Batchelor

Goulian

2003

Proc. Natl. Acad. Sci. U.S.A.

227

308

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“…phatase reactions (15). Known SHKs are obligate dimers and typically consist of an N-terminal sensor module and a C-terminal effector module, which comprises the dimerization/histidine phosphotransfer (DHp) and catalytic/ATP-binding (CA) domains.…”

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confidence: 99%

Charting the Signal Trajectory in a Light-Oxygen-Voltage Photoreceptor by Random Mutagenesis and Covariance Analysis

Gleichmann

Diensthuber

Möglich

2013

Journal of Biological Chemistry

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Background: Modular receptors like the photoreceptor YF1 detect signals and process them into biological responses. Results: We identify numerous residues in the photosensor module of YF1 governing signal detection and processing. Conclusion: Spatial clustering of these residues delineates structurally contiguous regions in the photosensor crucially involved in signal transduction. Significance: The underlying mechanistic principles are widely shared in signal receptors.

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“…For active kinase activity, the SK binds ATP and phosphorylates itself on a conserved histidine residue. The phosphoryl group is then transferred to a conserved aspartate residue in the receiver domain of the cognate RR (Casino et al, 2010;Hoch, 2000;Russo & Silhavy, 1993). The RR often acts as a transcriptional regulator of genes functionally related to the detected stimulus (see Fig.…”

Section: Introductionmentioning

confidence: 99%

Genetic analysis of signal integration by the Sinorhizobium meliloti sensor kinase FeuQ

2015

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The essential tension: opposed reactions in bacterial two-component regulatory systems

Cited by 115 publications

References 26 publications

Robustness and the cycle of phosphorylation and dephosphorylation in a two-component regulatory system

Robustness and the cycle of phosphorylation and dephosphorylation in a two-component regulatory system

Charting the Signal Trajectory in a Light-Oxygen-Voltage Photoreceptor by Random Mutagenesis and Covariance Analysis

Genetic analysis of signal integration by the Sinorhizobium meliloti sensor kinase FeuQ

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