Global regulation by the seven-component Pi signaling system

Abstract

This review concerns how Escherichia coli detects environmental inorganic orthophosphate (P(i)) to regulate genes of the phosphate (Pho) regulon by the PhoR/PhoB two-component system (TCS). P(i) control by the PhoR/PhoB TCS is a paradigm of a bacterial signal transduction pathway in which occupancy of a cell surface receptor(s) controls gene expression in the cytoplasm. The P(i) signaling pathway requires seven proteins, all of which probably interact in a membrane-associated signaling complex. Our latest studies show that P(i) signaling involves three distinct processes, which appear to correspond to different states of the sensory histidine kinase PhoR: an inhibition state, an activation state, and a deactivation state. We describe a revised model for P(i) signal transduction of the E. coli Pho regulon.

Fig. 1

Domain organization of PhoR. TM, transmembrane-anchoring domain; CR, positively charged linker region; PAS, Per-Arnt-Sim domain; DHp, dimerization and histidine phosphoacceptor domain; CA, a catalytic domain.

Fig. 2

Model for transmembrane signal transduction by environmental P_i. The signaling processes of inhibition, activation, and deactivation are proposed to correspond to different states of PhoR: an inhibition state (PhoR^I), an activation state (PhoR^A), and a deactivation state (PhoR^D). The P_i binding protein PstS is fully saturated when P_i is in excess. Under these conditions, a signal is propagated to PhoR leading to formation of PhoR^I, which interferes with phosphorylation of PhoB. No such signal exists under conditions of P_i limitation (or absence of a Pst component), leading to formation of the default state PhoR^A which acts as a phospho-donor for autophosphorylation of PhoB. Following a period of P_i limitation, PhoR^D promotes dephosphorylation of phospho-PhoB. Formation of PhoR^D requires an increased amount of PhoU or PstB in addition to excess P_i.