Protein Connectivity in Chemotaxis Receptor Complexes

PLoS Comput Biol. 2015 Dec 8;11(12):e1004650. doi: 10.1371/journal.pcbi.1004650. eCollection 2015 Dec.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / chemistry
  • Bacterial Proteins / metabolism*
  • Chemotaxis / physiology*
  • Computer Simulation
  • Escherichia coli / chemistry
  • Escherichia coli / physiology*
  • Escherichia coli / ultrastructure
  • Escherichia coli Proteins / chemistry
  • Escherichia coli Proteins / metabolism*
  • Histidine Kinase
  • Membrane Proteins / chemistry
  • Membrane Proteins / metabolism*
  • Methyl-Accepting Chemotaxis Proteins
  • Models, Biological*
  • Models, Chemical
  • Models, Statistical
  • Protein Interaction Mapping / methods

Substances

  • Bacterial Proteins
  • CheW protein, E coli
  • Escherichia coli Proteins
  • Membrane Proteins
  • Methyl-Accepting Chemotaxis Proteins
  • Histidine Kinase
  • cheA protein, E coli