Molecular basis for the phosphorylation of bacterial tyrosine kinase Wzc

The regulation of polymerisation and translocation are of fundamental interest in biology. The Wzc class of integral membrane tyrosine autokinase proteins serve as the master regulators of the biosynthesis and export of some bacterial capsular and exopolysaccharides. These polysaccharides play essential roles in infection, defence, and some are important industrial products. Wzc monomers are comprised of a large periplasmic domain, two transmembrane helices and a C-terminal cytoplasmic kinase domain with a tyrosine-rich tail. Wzc functions through cycling the formation and dissociation of an octameric complex, driven by changes in the phosphorylation status of the tyrosine-rich tail. E. coli Wzc serves a model for the wider family and we have determined structures of intermediate states with different extents of phosphorylation. Structural and computational data reveal the pre-ordering of the tyrosine-rich tail, the molecular basis underlying the unidirectionality of phosphorylation events, and the underlying structural dynamics on how phosphorylation status is transmitted.