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Modelling molecular events in a small volume of living cytoplasm

Date: 
Monday 24th September 2001 - 13:40 to 14:40
Venue: 
INI Seminar Room 1
Session Title: 
Vertical Integration in Biology: From Molecules to Organisms
Abstract: 
In a recent study, we proposed an atomic level structure for a lattice of chemotaxis receptors in coliform bacteria (Shimizu et al. Nature Cell Biol .2: 792-796, 2000). A unique feature of this model was that it created a small compartment between the plasma membrane and an extended hexagonal lattice of the signaling proteins CheA and CheW. The proposed compartment is 20-30 nm deep, perhaps 300-500 nm wide, and contains a thicket of extended coiled-coils forming the cytoplasmic domains of the chemotactic receptors. The compartment is not closed, and should be freely accessible to cytoplasmic proteins diffusing in from the lateral borders or through 10 nm diameter pores in the hexagonal lattice. Despite the absence of sealed boundaries, however, there is reason to think that this minute volume of bacterial cytoplasm will be highly enriched in two diffusible proteins, CheR and CheB, which are responsible for adaptation in the bacterial system. We are currently using computational methods to explore the possible movement of these enzymes through the "adaptation compartment". In particular we examined the possibility that these molecules might progress from receptor to receptor by swinging from one flexible region to another, like a monkey swinging through trees ("molecular brachiation"). We also attempted to predict temporal changes in protein conformation within such a molecular lattice. Could conformational changes in one receptor spread to neighboring receptors? If so, by what route and what will be the likely consequences for cellular behavior? Conclusions reached in this analysis are likely to lead to a clearer picture of the physiology of the chemotactic response in bacteria. They will also provide clues to the operation of other "privileged compartments" in both bacteria and eucaryotic cells.
University of Cambridge Research Councils UK
    Clay Mathematics Institute London Mathematical Society NM Rothschild and Sons