5 research outputs found
Enzyme localization can drastically affect signal amplification in signal transduction pathways
Push-pull networks are ubiquitous in signal transduction pathways in both
prokaryotic and eukaryotic cells. They allow cells to strongly amplify signals
via the mechanism of zero-order ultrasensitivity. In a push-pull network, two
antagonistic enzymes control the activity of a protein by covalent
modification. These enzymes are often uniformly distributed in the cytoplasm.
They can, however, also be colocalized in space, for instance, near the pole of
the cell. Moreover, it is increasingly recognized that these enzymes can also
be spatially separated, leading to gradients of the active form of the
messenger protein. Here, we investigate the consequences of the spatial
distributions of the enzymes for the amplification properties of push-pull
networks. Our calculations reveal that enzyme localization by itself can have a
dramatic effect on the gain. The gain is maximized when the two enzymes are
either uniformly distributed or colocalized in one region in the cell.
Depending on the diffusion constants, however, the sharpness of the response
can be strongly reduced when the enzymes are spatially separated. We discuss
how our predictions could be tested experimentally.Comment: PLoS Comp Biol, in press. 32 pages including 6 figures and supporting
informatio
The switching dynamics of the bacterial flagellar motor
Many swimming bacteria are propelled by flagellar motors that stochastically
switch between the clockwise and counterclockwise rotation direction. While the
switching dynamics are one of the most important characteristics of flagellar
motors, the mechanisms that control switching are poorly understood. We present
a statistical-mechanical model of the flagellar rotary motor, which consists of
a number of stator proteins that drive the rotation of a ring of rotor
proteins, which in turn drives the rotation of a flagellar filament. At the
heart of our model is the assumption that the rotor protein complex can exist
in two conformational states corresponding to the two respective rotation
directions, and that switching between these states depends on interactions
with the stator proteins. This naturally couples the switching dynamics to the
rotation dynamics, making the switch sensitive to torque and speed. Another key
element of our model is that after a switching event, it takes time for the
load to build up, due to polymorphic transitions of the filament. Our model
predicts that this slow relaxation dynamics of the filament, in combination
with the load dependence of the switching frequency, leads to a characteristic
switching time, in agreement with recent observations.Comment: 7 pages, 6 figures, RevTeX
Differential Affinity and Catalytic Activity of CheZ in E. coli Chemotaxis
Push–pull networks, in which two antagonistic enzymes control the
activity of a messenger protein, are ubiquitous in signal transduction pathways.
A classical example is the chemotaxis system of the bacterium
Escherichia coli, in which the kinase CheA and the
phosphatase CheZ regulate the phosphorylation level of the messenger protein
CheY. Recent experiments suggest that both the kinase and the phosphatase are
localized at the receptor cluster, and Vaknin and Berg recently demonstrated
that the spatial distribution of the phosphatase can markedly affect the
dose–response curves. We argue, using mathematical modeling, that the
canonical model of the chemotaxis network cannot explain the experimental
observations of Vaknin and Berg. We present a new model, in which a small
fraction of the phosphatase is localized at the receptor cluster, while the
remainder freely diffuses in the cytoplasm; moreover, the phosphatase at the
cluster has a higher binding affinity for the messenger protein and a higher
catalytic activity than the phosphatase in the cytoplasm. This model is
consistent with a large body of experimental data and can explain many of the
experimental observations of Vaknin and Berg. More generally, the combination of
differential affinity and catalytic activity provides a generic mechanism for
amplifying signals that could be exploited in other two-component signaling
systems. If this model is correct, then a number of recent modeling studies,
which aim to explain the chemotactic gain in terms of the activity of the
receptor cluster, should be reconsidered