title: Protein Connectivity in Chemotaxis Receptor Complexes.
abstract: The chemotaxis sensory system allows bacteria such as Escherichia coli to swim towards nutrients and away from repellents. The underlying pathway is remarkably sensitive in detecting chemical gradients over a wide range of ambient concentrations. Interactions among receptors, which are predominantly clustered at the cell poles, are crucial to this sensitivity. Although it has been suggested that the kinase CheA and the adapter protein CheW are integral for receptor connectivity, the exact coupling mechanism remains unclear. Here, we present a statistical-mechanics approach to model the receptor linkage mechanism itself, building on nanodisc and electron cryotomography experiments. Specifically, we investigate how the sensing behavior of mixed receptor clusters is affected by variations in the expression levels of CheA and CheW at a constant receptor density in the membrane. Our model compares favorably with dose-response curves from in vivo Förster resonance energy transfer (FRET) measurements, demonstrating that the receptor-methylation level has only minor effects on receptor cooperativity. Importantly, our model provides an explanation for the non-intuitive conclusion that the receptor cooperativity decreases with increasing levels of CheA, a core signaling protein associated with the receptors, whereas the receptor cooperativity increases with increasing levels of CheW, a key adapter protein. Finally, we propose an evolutionary advantage as explanation for the recently suggested CheW-only linker structures.
authors.affiliation: Department of Physics and Astronomy, University of Heidelberg, Heidelberg, Germany.|Department of Life Sciences and Centre for Integrative Systems Biology and Bioinformatics, Imperial College London, London, United Kingdom.
authors.forename: Stephan
authors.initials: S
authors.lastname: Eismann
authors.affiliation: Department of Life Sciences and Centre for Integrative Systems Biology and Bioinformatics, Imperial College London, London, United Kingdom.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Endres
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D002633:Chemotaxis / Q000502:physiology*; D003198:Computer Simulation; D004926:Escherichia coli / Q000737:chemistry / Q000502:physiology* / Q000648:ultrastructure; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000378:metabolism*; D000071677:Histidine Kinase; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D000072236:Methyl-Accepting Chemotaxis Proteins; D008954:Models, Biological; D008956:Models, Chemical; D015233:Models, Statistical; D025941:Protein Interaction Mapping / Q000379:methods
chemical_list: D001426:Bacterial Proteins; C489103:CheW protein, E coli; D029968:Escherichia coli Proteins; D008565:Membrane Proteins; D000072236:Methyl-Accepting Chemotaxis Proteins; D000071677:Histidine Kinase; C000607608:cheA protein, E coli