Conserved domains in bacterial regulatory proteins that respond to environmental stimuli.

Bacteria respond to fluctuations in the concentrations of various solutes in their environment by modulating the expression of specific sets of genes. In response to changes in medium osmolarity, for example, Escherichia coli cells change the levels of the outer-membrane porin proteins OmpC and OmpF in a reciprocal manner; in response to nitrogen or phosphate limitation, the cells synthesize proteins that enable them to scavenge trace amounts of these compounds from the environment. Genetic studies of these and other responses suggest that they are controlled in part by two-component regulatory systems. Nucleotide sequence analysis of these regulatory genes has now revealed an unexpected degree of conservation among them. The pattern of protein sequence homology (see figure) suggests that during prokaryotic evolution, a two-component system has been continually adapted for sensing specific changes in the environment and transducing that information, usually to the transcriptional apparatus. One component of each system is thought to act as an environmental sensor (sensor component) that transmits a signal to the second component (regulatory component), which then effects the response. The systems include genes in E. coli responding to osmolarity (envZ/ompR), nitrogen limitation (ntrB/nfrC), phosphate limitation @hoR/phoS), and toxic compounds (changes in membrane proteins controlled by cpxA/sfrA); genes controlling the virulence of Agrobacterium tumefaciens in response to plant exudate (virA/virG); and genes activating the expression of the @dicarboxylate transport structural gene in response to C4-dicarboxylates in Rhizobium leguminosarum (dctB/dctD). As illustrated in the figure, about 200 amino acids of the C-terminal region (diagonal lines) are conserved among the proteins that act as sensors. In the regulators, about 120 amino acids of the N-terminal region (dark stippling) are conserved; as discussed below, subclasses of regulators show greater homology. This conservation suggests a model for signal transduction and provides insight into the functions of various domains of the sensor and regulator proteins.