Fig. 1.
Genetic organization of the walRKJ operon in S. pneumoniae and model of WalRKSpn TCS function in exponentially growing and stressed cells. (A). The co-transcribed walR (response regulator), walK (histidine kinase/phosphatase) and walJ (auxiliary protein) genes are drawn to scale at left. walR, but not walK or walJ, is essential under normal growth conditions. Domains in one subunit of the WalK histidine kinase are shown at right, including the single membrane-spanning domain, the HAMP (linker) and PAS (signaling) domains, the DHp (dimerization/histidine phosphorylation) domain, and the CA (ATPase) catalytic domain. Both WalK and WalJ are membrane associated, whereas WalR is cytoplasmic (Wayne et al., 2010). (B) Model for WalRK signaling and gene regulation from this study. In exponentially growing cells, ≈26% WalR is phosphorylated, and functions to stimulate a basal level of WalRK regulon expression that maintains normal growth. In unstressed cells, WalK functions mainly as a phosphatase that sets the amount of WalR~P and limits crosstalk by non-cognate sensor kinases. In cells subjected to wall stresses or limitation of the pcsB regulon gene (signal arrow), the phosphatase activity of WalK is reduced, possibly by binding of a ligand or protein to the PAS domain of WalK, and the WalK autokinase/phosphoryltransferase reactions lead to increased amounts of WalR~P and regulon expression. See text for additional details.