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. 1996 Mar 1;15(5):1028–1036.

Integration of multiple domains in a two-component sensor protein: the Bordetella pertussis BvgAS phosphorelay.

M A Uhl 1, J F Miller 1
PMCID: PMC449998  PMID: 8605872

Abstract

BvgS and BvgA, a two-component system, regulate virulence gene expression in Bordetella pertussis. BvgS is a transmembrane sensor protein that can autophosphorylate and phosphorylate BvgA. Phosphorylated BvgA activates transcription of virulence genes. The cytoplasmic region of BvgS contains three domains separated by alanine/proline-rich sequences--the transmitter, receiver and C-terminus. We report that the C-terminal domain, like the transmitter and receiver, is an essential part of the phosphorelay from BvgS to BvgA. The BvgS C-terminal domain is phosphorylated in trans via a phosphotransfer mechanism by the cytoplasmic portion of BvgS, and trans-phosphorylation of the C-terminal domain requires both the transmitter and receiver. We also demonstrate that phosphorylated, purified C-terminal domain alone is sufficient for phosphotransfer to BvgA. A point mutation in the C-terminal domain (His1172-->Gln) abolishes BvgS activity in vivo and eliminates detectable phosphorylation of BvgA in vitro. Activity of BvgS His 1172-->Gln could be restored by providing the wild-type C-terminal domain in trans. Our results indicate an obligatory role for an alternate phosphodonor module in the BvgAS phosphorelay.

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