Bacterial signal transduction network in a genomic perspective

Abstract

Bacterial signalling network includes an array of numerous interacting components that monitor environmental and intracellular parameters and effect cellular response to changes in these parameters. The complexity of bacterial signalling systems makes comparative genome analysis a particularly valuable tool for their studies. Comparative studies revealed certain general trends in the organization of diverse signalling systems. These include (i) modular structure of signalling proteins; (ii) common organization of signalling components with the flow of information from N-terminal sensory domains to the C-terminal transmitter or signal output domains (N-to-C flow); (iii) use of common conserved sensory domains by different membrane receptors; (iv) ability of some organisms to respond to one environmental signal by activating several regulatory circuits; (v) abundance of intracellular signalling proteins, typically consisting of a PAS or GAF sensor domains and various output domains; (vi) importance of secondary messengers, cAMP and cyclic diguanylate; and (vii) crosstalk between components of different signalling pathways. Experimental characterization of the novel domains and domain combinations would be needed for achieving a better understanding of the mechanisms of signalling response and the intracellular hierarchy of different signalling pathways.

Fig. 1

Structures of cyclic AMP (cAMP) and cyclic diguanylate (c-diGMP).

Fig. 2

Parallelism in structures of response regulators and intracellular signalling proteins. Transmission of environmental signals from sensory kinases to response regulators involves phosphorylation of Asp residues in their CheY-like receiver domains, which changes the conformation of this domain, liberating the downstream DNA-binding or enzymatic domains. Likewise, ligand (e.g. oxygen) binding by the cytoplasmic PAS and/or GAF domains (intracellular signal) changes the conformation of these domains, liberating the downstream DNA-binding or enzymatic domains. Domain names are as Table 2, with the exception of HisKin, indicating a histidine kinase, and Fis, a DNA-binding domain. The examples are taken from the recently sequenced genomes of Bradyrhizobium japonicum, Leptospira interrogans, Pseudomonas putida, Ralstonia eutropha, Shigella flexneri, Shewanella oneidensis and Thermosynechococcus elongatus. See Table 4 for more examples.