title: Central role of the BvgS receiver as a phosphorylated intermediate in a complex two-component phosphorelay.
abstract: Two-component systems use phosphorylation reactions to regulate stimulus/response pathways. In Bordetella pertussis, a human respiratory pathogen, the infectious cycle of the organism is controlled by the BvgAS two-component system. BvgS has similarities to sensor and response regulator components and is an autophosphorylating kinase that phosphorylates BvgA. BvgA, a response regulator, is a DNA-binding protein that activates virulence gene transcription. Three phosphorylated BvgS domains, the transmitter, receiver, and C terminus, are essential for signal transduction. We now demonstrate that the BvgS transmitter is sufficient for autophosphorylation but is unable to phosphorylate the C terminus or BvgA. The BvgS receiver regulates several phenotypes: dephosphorylation of both the BvgS transmitter and C terminus as well as transfer of a phosphoryl group from the transmitter to the C terminus. Our results indicate that BvgAS signal transduction initiates with autophosphorylation of the transmitter followed by phosphotransfer to the receiver. The phosphorylated receiver can donate to the C terminus or to water. The phosphorylated C terminus is then able to transfer the phosphoryl group to BvgA.
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, UCLA, Los Angeles, California 90024, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Uhl
authors.forename: J F
authors.initials: JF
authors.lastname: Miller
mesh_terms: D018528:ATP-Binding Cassette Transporters; D001426:Bacterial Proteins / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D015246:Deoxyribonuclease EcoRI / Q000378:metabolism; D015247:Deoxyribonuclease HindIII / Q000378:metabolism; D004926:Escherichia coli; D029968:Escherichia coli Proteins; D006801:Humans; D058619:Maltose-Binding Proteins; D008954:Models, Biological; D009004:Monosaccharide Transport Proteins; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D018528:ATP-Binding Cassette Transporters; D001426:Bacterial Proteins; D002352:Carrier Proteins; D029968:Escherichia coli Proteins; D058619:Maltose-Binding Proteins; D009004:Monosaccharide Transport Proteins; D014157:Transcription Factors; C080662:bvgS protein, Bordetella pertussis; C461599:maltose transport system, E coli; D015246:Deoxyribonuclease EcoRI; D015247:Deoxyribonuclease HindIII