POSTERS - BLAST X - University of Utah

BLAST X Poster #16
MODELING SCAFFOLD PHOSPHORYLATION AS AN ADAPTATION MECHANISM IN
BACTERIAL CHEMOTAXIS
Roger Alexander, Adam Bildersee, and Thierry Emonet
Department of Molecular, Cellular, and Developmental Biology, Kline Biology Tower 1054, Yale
University, New Haven, CT 06520
Bacterial chemotaxis is one of the best-understood signaling networks in biology.
Chemotaxis in E. coli is a model system for thoroughly understanding a behavioral phenotype at
the molecular level. Chemotaxis has been studied experimentally in a variety of other species,
and modeled in B. subtilis, but no dynamical models of chemotaxis network architectures from
other species have yet been built. A key feature of the chemotaxis signal transduction network
is adaptation: after a transient response to a step change in input stimulus, its activity returns to
its pre-stimulus steady state level, allowing the system to respond to higher stimulus
concentrations without saturation. In E. coli, adaptation is mediated through two enzymes, CheR
and CheB, that methylate and demethylate the sensory receptors. In this work we consider
scaffold phosphorylation as an adaptation mechanism complementary to receptor methylation.
The receptors form a sensory array in the membrane at the cell pole; the scaffold protein
couples the receptors to the kinase CheA which they activate. In all current dynamical models of
chemotaxis, the receptors, scaffolds, and kinases are treated as a single species, a receptorkinase
complex. This is understandable, because in E. coli, the scaffold CheW is a passive
mediator of the receptor-kinase interaction. However, in other organisms, the scaffold CheV
has not only a CheW scaffold domain, but also a receiver domain that is the target of
phosphorylation by the kinase. Bacillus subtilis has both CheW and CheV scaffolds, and
phosphorylation of CheV is known to be necessary for adaptation. In B. subtilis, phospho-CheV
decouples receptor from kinase, so it actively mediates their interaction. The evolutionary
distance between B. subtilis and E. coli is wide, and there are other differences between their
chemotaxis network architectures that confound an understanding of the specific role of scaffold
phosphorylation. Therefore we choose to focus on a close relative of E. coli, Salmonella
enterica serovar typhimurium. The chemotaxis network architecture in Salmonella is almost
identical to that in E. coli, except that Salmonella has both CheW and CheV scaffolds. A mutant
Salmonella that lacks methylation-based adaptation is able to adapt partially, presumably
through its scaffold phosphorylation mechanism. We have built a dynamical model of the
chemotaxis network in E. coli that explicitly represents receptor-kinase coupling by the scaffold.
We have extended that model to include scaffold phosphorylation in Salmonella. Our model of a
Salmonella mutant that lacks methylation exhibits partial adaptation, consistent with
experimental results. This work is the first step in a long-range program to explore how
evolutionary changes in chemotaxis network architecture affects the dynamics and function of
the network. Evolution of dynamic signal transduction networks is an important emerging
research area in systems biology.
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