I propose to study and model the protein-protein interactions that underlie sensory-motor regulation in motile cells such as E. coli and S. typhimurium. These cells chemotax towards attractants and away from repellents. The mechanism for this behavior involves membrane spanning chemoreceptors that regulate a histidine kinase, CheA, to control the phosphorylation of the response regulator, CheY. Phospho-CheY binds the flagellar motor proteins to change the direction of swimming. It is now known that the chemoreceptors and other components of this system are localized to a small patch near one pole of the cell. I propose first, to understand better using fluorescence resonance energy transfer and molecular modeling the interactions that exist between the chemoreceptors CheA, and CheW; second, to similarly determine where CheA and CheW interact, and whether they interact in the absence of the chemoreceptors; and third, to develop an information theoretical model to understand the information transmission and processing capabilities of the chemotaxis system. In addition to the general significance of the chemotaxis system to transmembrane receptor signaling, the underlying mechanism provides a model for understanding homologous two-component systems that mediate adaptations to environmental perturbations ranging from cell cycle regulation to fruiting body development and sporulation in bacteria and a range of other organisms.
| Webre, Daniel J; Wolanin, Peter M; Stock, Jeffry B (2004) Modulated receptor interactions in bacterial transmembrane signaling. Trends Cell Biol 14:478-82 |
| Francis, Noreen R; Wolanin, Peter M; Stock, Jeffry B et al. (2004) Three-dimensional structure and organization of a receptor/signaling complex. Proc Natl Acad Sci U S A 101:17480-5 |
| Park, Sungsu; Wolanin, Peter M; Yuzbashyan, Emil A et al. (2003) Motion to form a quorum. Science 301:188 |
| Napper, Scott; Wolanin, Peter M; Webre, Daniel J et al. (2003) Intramolecular rearrangements as a consequence of the dephosphorylation of phosphoaspartate residues in proteins. FEBS Lett 538:77-80 |
| Wolanin, Peter M; Webre, Daniel J; Stock, Jeffry B (2003) Mechanism of phosphatase activity in the chemotaxis response regulator CheY. Biochemistry 42:14075-82 |
| Wolanin, Peter M; Thomason, Peter A; Stock, Jeffry B (2002) Histidine protein kinases: key signal transducers outside the animal kingdom. Genome Biol 3:REVIEWS3013 |
| Da Re, Sandra; Tolstykh, Tatiana; Wolanin, Peter M et al. (2002) Genetic analysis of response regulator activation in bacterial chemotaxis suggests an intermolecular mechanism. Protein Sci 11:2644-54 |
