CENTRAL ROLE OF THE BVGS RECEIVER AS A PHOSPHORYLATED INTERMEDIATE INA COMPLEX 2-COMPONENT PHOSPHORELAY

Two-component systems use phosphorylation reactions to regulate stimul us/response pathways. In Bordetella pertussis, a human respiratory pat hogen, the infectious cycle of the organism is controlled by the BvgAS two-component system. BvgS has similarities to sensor and response re gulator components and is an autophosphorylating kinase that phosphory lates BvgA. BvgA, a response regulator, is a DNA-binding protein that activates virulence gene transcription. Three phosphorylated BvgS doma ins, the transmitter, receiver, and C terminus, are essential for sign al transduction. We now demonstrate that the BvgS transmitter is suffi cient for autophosphorylation but is unable to phosphorylate the C ter minus or BvgA. The BvgS receiver regulates several phenotypes: dephosp horylation of both the BvgS transmitter and C terminus as well as tran sfer of a phosphoryl group from the transmitter to the C terminus. Our results indicate that BvgAS signal transduction initiates with autoph osphorylation of the transmitter followed by phosphotransfer to the re ceiver. The phosphorylated receiver can donate to the C terminus or to water. The phosphorylated C terminus is then able to transfer the pho sphoryl group to BvgA.