Hysteretic and graded responses in bacterial two-component signal transduction
Issue date
2008Suggested 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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Show full item recordAbstract
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.