The unorthodox two-component phosphorelay systems BvgAS and EvgAS of Bordet
ella pertussis and E. coli, respectively, are suitable model systems to inv
estigate the molecular basis of signalling specificity, because, despite th
eir high relatedness on the sequence level, they do nor cross-talk to each
other. We could show that the two systems belong to the obligate type of ph
osphorelay systems and that signalling specificity is mediated by the HPt m
odules of the histidine kinases and the receiver domains of the effector pr
oteins. To gain more insight into signalling specificity on the molecular l
evel, we started a detailed structural analysis of the respective proteins
using a combination of genetic and biochemical methods including limited pr
oteolysis and chemical modification of purified proteins and their mass spe
ctrometrical analysis.