Evolution of Two-Component Signal Transduction

Abstract

Two-component signal transduction (TCST) systems are the principal means for coordinating responses to environmental changes in bacteria as well as some plants, fungi, protozoa, and archaea. These systems typically consist of a receptor histidine kinase, which reacts to an extracellular signal by phosphorylating a cytoplasmic response regulator, causing a change in cellular behavior. Although several model systems, including sporulation and chemotaxis, have been extensively studied, the evolutionary relationships between specific TCST systems are not well understood, and the ancestry of the signal transduction components is unclear. Phylogenetic trees of TCST components from 14 complete and 6 partial genomes, containing 183 histidine kinases and 220 response regulators, were constructed using distance methods. The trees showed extensive congruence in the positions of 11 recognizable phylogenetic clusters. Eukaryotic sequences were found almost exclusively in one cluster, which also showed the greatest extent of domain variability in its component proteins, and archaeal sequences mainly formed species-specific clusters. Three clusters in different parts of the kinase tree contained proteins with serine-phosphorylating activity. All kinases were found to be monophyletic with respect to other members of their superfamily, such as type II topoisomerases and Hsp90. Structural analysis further revealed significant similarity to the ATP-binding domain of eukaryotic protein kinases. TCST systems are of bacterial origin and radiated into archaea and eukaryotes by lateral gene transfer. Their components show extensive coevolution, suggesting that recombination has not been a major factor in their differentiation. Although histidine kinase activity is prevalent, serine kinases have evolved multiple times independently within this family, accompanied by a loss of the cognate response regulator(s). The structural and functional similarity between TCST kinases and eukaryotic protein kinases raises the possibility of a distant evolutionary relationship.

Multidrug resistant Acinetobacter baumannii--the role of AdeABC (RND family) efflux pump in resistance to antibiotics.

“…2). Two-component system are signal transduction pathways in bacteria that respond to environmental conditions (pump is dependent on substrate) [50,73,75]. The protein AdeR (regulator) consisted of 228 amino acids is typical transcriptional regulator and protein AdeS (sensor kinase) is shorter and demonstrate activity of bacterial histidine kinase, that work together to regulate target gene expression in response to stimuli.…”

“…Phosphorilation of each domain and the transfer of phosphoryl groups between these domains is reversible by the phosphatase activity of the sensor. The histidine kinases leads to a switch between phosphorylation and dephosphorylation activities and modulates the active state of the regulators, which controls structural genes expression [9,50,138].…”

Comparative analysis of two-component signal transduction systems of Bacillus cereus, Bacillus thuringiensis and Bacillus anthracis

“…To uncover the signal transduction routes in which these 'orphans' are involved, we compared the NJ trees (the HK and RR trees described above) of the interacting domains and coupled 'orphans' on the basis of cognate clustering within these trees. This method was successfully employed by us before (C. Francke and others, unpublished results) and it has been shown that HKs and RRs that are known to interact fall into corresponding phylogenetic subfamilies (Grebe & Stock, 1999;Koretke et al, 2000).…”

Bacterial sensor kinase TodS interacts with agonistic and antagonistic signals

“…In fact, genes encoding TCSs are present in almost all bacteria and typically represent Յ1% of their genomes (1,2). TCSs are also present, although to a lesser extent, in archaea and eukaryotes such as fungi, slime molds, and plants (3,4). These systems are often made up of a histidine protein kinase (HPK) and a response regulator (RR).…”