Modeling of Signal Transduction
for Bacterial Chemotaxis
Using the E-CELL Simulation System

Yuri Matsuzaki 12
yuri@sfc.keio.ac.jp
Tom Shimizu 14
tom@sfc.keio.ac.jp1234

1Kanako Saito 13
t95401ks@sfc.keio.ac.jp
Masaru Tomita 13
mt@sfc.keio.ac.jp

Laboratory for Bioinformatics
Graduate School of Media and Governance
Department of Environmental Information
Keio University, 5322 Endo, Fujisawa 252-8520, Japan
Department of Zoology, Cambridge University, CB2 E3J UKIntroduction

We have modeled signal transduction for bacterial chemotaxis using the E-CELL system, a genericsoftware for simulation of cellular processes [3]. Chemotaxis is the orientation of an organism inrelation to the presence of a particular chemical. The chemotactic response of E. coli depends on theability to modulate their agellar motor in response to external stimuli. The agellar motor has aswitch protein which interacts with proteins called CheY. The CheY protein in a phosphorylated form
is known to bind with the motor up to 20-fold more frequently than that in an unphosphorylatedform. In this way, the phosphorylation controls bacterial response to external stimuli by regulating
binding anity of the CheY protein and the motor switch.
The external stimulus bound to a bacterial receptor works as a initial control element of cytoplasmic
phosphorylation cascade. In case that the stimulus is an attractant, the phosphorylation ow issuppressed and, consequently, the motor rotates counterclockwise, resulting in smooth swim.
2

Simulation with the E-CELL system

We have simulated the phosphorylation cascade for bacterial (E.coli) chemotaxis with the attractant
being aspartate (Fig. 1). In the E-CELL system, each reaction is de ned as a set of substrates,products, catalysts, and kinetic constants. We use the following three kinetic types:
 Molecular binding, such as receptor-ligand interaction and CheY-motor binding, is modeledusing `EqReactor' type, which computes equilibrium state from the equilibrium constants.

 Autophosphorylation of proteins, such as CheA, CheB and CheY, is modeled using `Michaelis-MentenReactor' type, which calculates the velocity using the Michaelis-Menten equation withthe constants, Km and Kcat.

 Autodephosphorylation of the proteins is modeled using `PlainReactor' type, whose velocity is

proportional to the substrate's concentration.

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Aspartate
Motor
Tar
CheW
PP
CheB

CheB
Pi

CheA

CheYATP

HOAc

ADP

POAc

CheA

CheW

CheYP

Pi

Figure 1: Signal transduction for bacterial chemotaxis.
3

Discussion

The E-CELL system allows us to perform virtual experiments on the bacterial chemotaxis model wehave constructed. For example, mutants of the model can be created by making a particular proteinalways zero. The simulated behavior of each mutant, as well as the wild type, can then be comparedwith the results of laboratory experiments with indexes such as swimming direction, response time,and phosphate ux. We also compare our results with other simulation systems [1, 2].
Acknowledgements

This work was supported in part by a Grant-in-Aid for Scienti c Research on Priority Areas `Genome
Science' from The Ministry of Education, Science, Sports and Culture in Japan.
References[1] Bray, D., Bourret, R.B., and Simon, M.I., Computer Simulation of the Phosphorylation Cascade
Controlling Bacterial Chemotaxis, Molecular Biology of the Cell, 4:469{482, 1993.
[2] Bray, D. and Bourret, R.B., Computer analysis of the binding reactions leading to a transmembrane receptor-linked multiprotein complex involved in bacterial chemotaxis, Molecular Biologyof the Cell, 6:1367{1380, 1995.
[3] Tomita, M., Hashimoto, K., Takahashi, K., Shimizu, T., Matsuzaki, Y., Miyoshi, F., Saito, K.,Tanida, S., Yugi, K., Venter, J.C., and Hutchison, C., E-CELL: Software environment for wholecell simulation, Bioinformatics, (to appear).

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