New Insights into the Non-orthodox Two Component Rcs Phosphorelay System

Abstract

The Rcs phosphorelay system, a non-orthodox two-component regulatory system, integrates environmental signals, regulates gene expression, and alters the physiological behavior of members of the Enterobacteriaceae family of Gram-negative bacteria. Recent studies of Rcs system focused on protein interactions, functions, and the evolution of Rcs system components and its auxiliary regulatory proteins. Herein we review the latest advances on the Rcs system proteins, and discuss the roles that the Rcs system plays in the environmental adaptation of various Enterobacteriaceae species.

Keywords: Rcs phosphorelay system; acetylation; auxiliary regulators; envelope stress; molecular evolution.

FIGURE 1

The Rcs phosphorelay system in E. coli. (A) Regulation of RcsB phosphorylation in E. coli. Left: in the absence of stress, RcsF is funneled by BamA and sequestered by OmpA as a surface-exposed protein. YrfF (IgaA in S. enterica serovar Typhimurium) inhibits the kinase activity of RcsC, resulting in dephosphorylation of RcsB. In this situation, AcP might act as a phosphoryl group donor to keep a low level of RcsB phosphorylation. Right: in the presence of stress, RcsF does not interact with BamA and OmpA but interacts with IgaA that release the inhibition of YrfF (IgaA in S. enterica serovar Typhimurium). RcsC autophosphorylates at the H1 position of its HK domain in an ATP-dependent manner. The phosphoryl group is then transferred to D1 on the PR domain of RcsC, then to H2 on the HPt domain of RcsD and finally to RcsB. (B) The homo- and heterodimers of RcsB in E. coli. Left: RcsB forms homodimer or heterodimer with RcsA to regulate target genes in a phosphorylation dependent manner. Right: RcsB forms heterodimer with BglJ, GadE, or MatA to regulate target genes in a phosphorylation independent manner. OM, outer membrane; PM, periplasm; IM, inner membrane; CM, cytoplasm; PG, peptidoglycan; P, phosphoryl group.