Spatial organization of the bacterial chemotaxis system
Introduction
Chemotaxis enables bacteria to find favourable growth conditions by migrating towards higher concentrations of attractants (e.g. sugars and amino acids), while simultaneously avoiding repellents (e.g. potentially harmful chemicals). The chemotactic response represents a paradigm of a simple signalling system and, despite its relative simplicity, shows remarkable sensitivity and robustness. It is mediated by a two-component signal transduction pathway, with the histidine kinase CheA and the response regulator CheY being the two central proteins. Together with the ‘adaptor’ protein CheW, CheA associates with either membrane or cytoplasmic chemosensory receptors. Ligand-binding to receptors regulates the autophosphorylation activity of CheA in these ternary complexes. The CheA phosphoryl group is subsequently transferred to CheY, which then diffuses away to the flagellum where it modulates motor rotation. Adaptation to continuous stimulation is mediated by the methyltransferase CheR and the methylesterase CheB, which tune the ability of receptors to activate CheA by adjusting their level of methylation, and precisely return activity of CheA to its pre-stimulus state. Together, CheA, CheW, CheR and CheB represent an evolutionarily conserved core of the pathway, which is common to most chemotactic bacteria and archaea. The C-terminal signalling part of receptors is also highly conserved, whereas their N-terminal sensory domains are variable. The number of receptor types with unique sensory domains defines the chemoeffector detection profile of an organism. Along with these core components, most chemotaxis pathways possess additional enzymes to accelerate CheY dephosphorylation and/or assist adaptation [1].
Escherichia coli has a relatively simple chemotaxis system, with only five types of membrane-associated receptors and one additional enzyme, the phosphatase CheZ. It has been extensively studied on the structural, genetic and biochemical level and became one of the favourite systems for computer modelling of signal transduction (see [2, 3, 4, 5, 6, 7] for recent reviews). However, the importance of the spatial organization of the chemotaxis pathway has long been underappreciated. We discuss, with an emphasis on E. coli, recent advances in the understanding of the formation of the chemosensory clusters, their localization within cells and their function in signal transduction.
Section snippets
Organization of the sensory complex
The central processing unit in the chemotaxis machinery is the ternary complex of receptors, CheW and CheA (Figure 1), to which the remaining proteins localize by interaction with receptors (CheR) or CheA (CheY, CheB and CheZ). Despite intensive research, the architecture of the ternary complex remains poorly understood. Early biochemical studies suggested that the receptor–CheA interaction depends on CheW, which led to a model of one CheA dimer being linked to one receptor dimer by two CheW
Cluster positioning and segregation
Receptor clusters in E. coli can be classified as polar or lateral, according to their localization in the cell (Figure 2). Polar localization seems to be an intrinsic property of chemoreceptors, independent of other chemotaxis proteins [20••]. It is not the result of directed membrane insertion, because a fusion of the Tar receptor to a green fluorescent protein (GFP) was shown to be initially inserted into the lateral membrane and only subsequently become trapped at the pole [30•]. The nature
Stability and functional importance of clusters
Receptor–CheW–CheA complexes are believed to be stable on the time scale of chemotactic signalling [36]. There is some evidence that attractant binding or demethylation of receptors decreases cluster stability [37, 38], but these effects appear to be minor in vivo [39, 40, 41, 42], although ligand binding might influence the relative arrangement of and distances between receptors in the lattice [16, 43••]. Association of the other chemotaxis proteins with the ternary complex is believed to be
Conclusions
Receptor clustering appears to benefit bacterial chemotaxis in several ways. Although the precise molecular architecture of clusters remains to be resolved, it has become clear that interactions between the cytoplasmic parts of receptors are the decisive factor in the formation of clusters and in their functioning. It can be speculated that increasing the repertoire of chemoeffectors, whilst integrating all stimuli into one coherent response, was the main driving force in the evolution of the
References and recommended reading
Papers of particular interest, published within the annual period of review, have been highlighted as:
• of special interest
•• of outstanding interest
Acknowledgements
Research in our laboratory is supported by grants SO 421/3-1 and SO 421/6-1 from Deutsche Forschungsgemeinschaft and by a grant RGP 66/2005 from the Human Frontier Science Foundation. We thank JS Parkinson, TS Shimizu, NS Wingreen and S Thiem for helpful discussions.
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