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Hysteretic and graded responses in bacterial two-component signal transduction

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Issue date
2008
Author
Igoshin, Oleg A.
Alves, Rui
Savageau, Michael A.
Suggested citation
Igoshin, Oleg A.; Alves, Rui; Savageau, Michael A.; . (2008) . Hysteretic and graded responses in bacterial two-component signal transduction. Molecular Microbiology, 2008, vol. 68, p. 1196-1215. https://doi.org/10.1111/j.1365-2958.2008.06221.x.
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Abstract
Bacterial two-component systems (TCS) are key signal transduction networks regulating global responses to environmental change. Environmental signals may modulate the phosphorylation state of sensor kinases (SK). The phosphorylated SK trans- fers the phosphate to its cognate response regulator (RR), which causes physiological response to the signal. Frequently, the SK is bifunctional and, when unphosphorylated, it is also capable of dephosphory- lating the RR. The phosphatase activity may also be modulated by environmental signals. Using the EnvZ/ OmpR system as an example, we constructed math- ematical models to examine the steady-state and kinetic properties of the network. Mathematical modelling reveals that the TCS can show bistable behaviour for a given range of parameter values if unphosphorylated SK and RR form a dead-end complex that prevents SK autophosphorylation. Addi- tionally, for bistability to exist the major dephospho- rylation flux of the RR must not depend on the unphosphorylated SK. Structural modelling and pub- lished affinity studies suggest that the unphosphory- lated SK EnvZ and the RR OmpR form a dead-end complex. However, bistability is not possible because the dephosphorylation of OmpR ~ P is mainly done by unphosphorylated EnvZ. The implications of this potential bistability in the design of the EnvZ/OmpR network and other TCS are discussed.
URI
http://hdl.handle.net/10459.1/57054
DOI
https://doi.org/10.1111/j.1365-2958.2008.06221.x
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Molecular Microbiology, 2008, vol. 68, p. 1196-1215
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