EnvZ is an inner membrane-bound histidine kinase that functions as an osmotic sensor capable of phosphorylating the regulator protein, OmpR. The natural ligand that activates EnvZ has not been identified as yet although it is suggested that EnvZ somehow senses membrane curvature or fluidity.
EnvZ contains a C-terminal transmitter module and an N-terminal periplasmic domain flanked by membrane-spanning segments. There are two transmembrane domains, a periplasmic domain consisting of 115 residues, and a 270 residue cytoplasmic domain. The role of the periplasmic domain is unclear although circular dichroism analysis (Lys-48 to Arg-162) shows that it consists of 35% alpha helices and 16% beta sheets. In fact, EnvZ has dual opposing enzymatic activities; OmpR-phosphorylase (kinase) and phospho-OmpR-dephosphorylase (phosphatase). The osmotic signal is proposed to regulate the ratio of the kinase to the phosphatase activities of EnvZ to modulate the level of OmpR phosphorylation.
High osmolarity promotes autophosphorylation, leading to an increase in OmpR phosphorylation, whilst low osmolarity promotes dephosphorylation. These dual activities of EnvZ presumably represent different conformational states of the molecule. His-243 is the major site of phosphorylation of EnvZ. There is evidence that EnvZ is a dimer in the cell. If this is the case, then a model may be proposed for the sensing of the signal at the membrane through direct interaction between the transmembrane domains. Membrane alterations, induced by increased osmolarity, could cause movement of the transmembrane domains of EnvZ relative to one another. Inducing conformational changes within the linker and cytoplasmic domains could subsequently propagate the signal generated by modulating interactions between the transmembrane domains. In turn, this would modulate the enzymatic activities of EnvZ.