Working model for VanRA-VanSA signaling.
A schematic view is shown for the VanSA protein. The protein comprises three domains: The sensor domain (gray), which includes two predicted transmembrane helices and is responsible for sensing the inducing signal; the dimerization & histidine-phosphotransfer (DHp) domain (green), which includes the conserved histidine that is the site of autophosphorylation; and the catalytic (CA) domain (magenta), which binds nucleotide triphosphate and is responsible for catalyzing histidine phosphorylation. In the absence of vancomycin, VanSA acts as a phosphatase, keeping VanRA in an inactive, dephosphorylated state. Vancomycin induces VanSA to autophosphorylate, after which phospho-VanSA transfers the phosphoryl group to VanRA. Finally, phospho-VanRA activates transcription of the van resistance genes.