E. coli Etk

Wzc/Etk proteins are inner-membrane PTKs in Gram-negative bacteria, with two trans-membrane α-helices separating the N-terminal periplasmic and C-terminal cytoplasmic domains. This arrangement somewhat resembles the eukaryotic receptor PTKs despite the absence of any significant sequence homology between them. The ∼270-residue cytoplasmic domains of Wzc/Etk contain the ATP-binding Walker-A and Walker-B motifs, and a Tyr-rich cluster (5–7 Tyr in a 12-residue stretch) at the C-terminus. Wzc/Etk phosphorylation proceeds through a cooperative, two-step mechanism involving both intra- and inter-phosphorylation. First, a key upstream Tyr residue is autophosphorylated through an intra-molecular process, which results in protein kinase activation. Subsequently, the clustered C-terminal Tyr residues undergo inter-molecular phosphorylation. Wzc has been shown to harbour ATPase activity, which is enhanced by intra-phosphorylation at this Tyr residue as well.