Novel domains of the prokaryotic two-component signal transduction systems

Abstract

The archetypal two-component signal transduction systems include a sensor histidine kinase and a response regulator, which consists of a receiver CheY-like domain and a DNA-binding domain. Sequence analysis of the sensor kinases and response regulators encoded in complete bacterial and archaeal genomes revealed complex domain architectures for many of them and allowed the identification of several novel conserved domains, such as PAS, GAF, HAMP, GGDEF, EAL, and HD-GYP. All of these domains are widely represented in bacteria, including 19 copies of the GGDEF domain and 17 copies of the EAL domain encoded in the Escherichia coli genome. In contrast, these novel signaling domains are much less abundant in bacterial parasites and in archaea, with none at all found in some archaeal species. This skewed phyletic distribution suggests that the newly discovered complexity of signal transduction systems emerged early in the evolution of bacteria, with subsequent massive loss in parasites and some horizontal dissemination among archaea. Only a few proteins containing these domains have been studied experimentally, and their exact biochemical functions remain obscure; they may include transformations of novel signal molecules, such as the recently identified cyclic diguanylate. Recent experimental data provide the first direct evidence of the participation of these domains in signal transduction pathways, including regulation of virulence genes and extracellular enzyme production in the human pathogens Bordetella pertussis and Borrelia burgdorferi and the plant pathogen Xanthomonas campestris. Gene-neighborhood analysis of these new domains suggests their participation in a variety of processes, from mercury and phage resistance to maintenance of virulence plasmids. It appears that the real picture of the complexity of phosphorelay signal transduction in prokaryotes is only beginning to unfold.

Bacterial c-di-GMP Is an Immunostimulatory Molecule

“…The cyclic dinucleotide c-di-GMP is now recognized as a widespread intracellular signaling molecule in prokaryotes (2,3,(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). We have explored the extracellular biological effects of c-di-GMP and its potential use as a therapeutic agent.…”

“…The level of intracellular c-di-GMP in some species is believed to be regulated by the opposing effects of diguanylate cyclases for c-di-GMP synthesis from GTP and c-di-GMP phosphodiesterase for breakdown to 5Ј-GMP and each controlling the level of c-di-GMP in the cell. c-di-GMP has been shown to influence bacterial cell survival, cell differentiation, colonization and biofilm formation, as well as bacteria-host interactions (2,3,(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). Although the role of intracellular c-di-GMP in bacteria is now recognized and is becoming an intense field of research, we have been studying the effect of this microbial molecule in the context of other biological systems and its potential clinical and therapeutic use for the prevention and inhibition of infection and disease (19 -22).…”

The structure–function relationship of WspR, a Pseudomonas fluorescens response regulator with a GGDEF output domain

“…An analysis of sequence conservation among GGDEF domains (Galperin et al, 2001) has indicated that aspartate and glutamate are found with similar frequency at position 250. It is possible that the conformational constraints on the first glutamate in the RYGGEEF motif are not so pronounced as for the second, allowing aspartate or glutamate to be present.…”

“…The GGDEF domain was first recognized in PleD, a response regulator responsible for mediating the swarmer-to-stalked cell transition in C. crescentus (Hecht & Newton, 1995), and has since been identified in large numbers in many bacterial species (Galperin et al, 1999(Galperin et al, , 2001Galperin, 2005). GGDEF domains are often associated with receiver, PAS and GAF sensor domains, and are frequently paired with EAL domains (Galperin et al, 2001).…”

“…GGDEF domains are often associated with receiver, PAS and GAF sensor domains, and are frequently paired with EAL domains (Galperin et al, 2001).…”