a one-way concentration gradient of glucose. The HPr is common to the phosphotransferase systems of the other substrates mentioned earlier, as is the upstream EI. Proteins downstream of HPr tend to vary between the different sugars. The transfer of a phosphate group to the substrate once it has been imported through the membrane transporter prevents the transporter from recognizing the substrate again, thus maintaining a concentration gradient that favours further import of the substrate through the transporter. Specificity. In many bacteria, there are four different sets of IIA, IIB, and IIC proteins, each specific for a particular sugar (glucose, mannitol, mannose, and lactose/chitobiose). To make things more complicated, IIA may be fused to IIB to form a single protein with 2 domains, or IIB may be fused to IIC (the transporter), also with 2 domains. Regulation. With the glucose phosphotransferase system, the phosphorylation status of EIIA can have regulatory functions. For example, at low glucose concentrations phosphorylated EIIA accumulates and this activates membrane-bound adenylate cyclase. Intracellular cyclic AMP levels rise and this then activates CAP (catabolite activator protein), which is involved in the catabolite repression system, also known as glucose effect. When the glucose concentration is high, EIIA is mostly dephosphorylated and this allows it to inhibit adenylate cyclase, glycerol kinase, lactose permease, and maltose permease. Thus, as well as the PEP group translocation system being an efficient way to import substrates into the bacterium, it also links this transport to regulation of other relevant proteins. Structural analysis Three-dimensional structures of examples of all the soluble, cytoplasmic complexes of the PTS were solved by G. Marius Clore using multidimensional NMR spectroscopy, and led to significant insights into how signal transduction proteins recognize multiple, structurally dissimilar partners by generating similar binding surfaces from completely different structural elements, making use of large binding surfaces with intrinsic redundancy, and exploiting side chain conformational plasticity. References External links Enzymes