PTS EIIA type-2 domain (PTS_EIIA_type-2_dom)
Type: Domain

The phosphoenolpyruvate-dependent sugar phosphotransferase system (PTS) is a major carbohydrate transport system in bacteria. The PTS catalyses the phosphorylation of incoming sugar substrates concomitant with their translocation across the cell membrane. The general mechanism of the PTS is the following: a phosphoryl group from phosphoenolpyruvate (PEP) is transferred to enzyme I (EI) of PTS which in turn transfers it to a phosphoryl carrier protein (HPr). Phospho-HPr then transfers the phosphoryl group to a sugar-specific permease which consists of at least three structurally distinct domains (IIA, IIB, and IIC), which can either be fused together in a single polypeptide chain or exist as two or three interactive chains, formerly called enzymes II (EII) and III (EIII).

The first domain (IIA) , carries the first permease-specific phosphorylation site, an histidine which is phosphorylated by phospho-HPr. The second domain (IIB) is phosphorylated by phospho-IIA on a cysteinyl or histidyl residue, depending on the sugar transported. Finally, the phosphoryl group is transferred from the IIB domain to the sugar substrate concomitantly with the sugar uptake processed by the IIC domain. The IIC domain forms the translocation channel and at the specific substrate-binding site. An additional transmembrane domain IID, homologous to IIC, can be found in some PTSs, e.g. for mannose .

According to structural and sequence analyses, the PTS EIIA domain can be divided in five groups .

The PTS EIIA type 1 domain, which is found in the Glucose class of PTS, has an average length of about 100 amino acids. It forms an antiparallel β-barrel structure that incorporates 'Greek key' and 'jellyroll' topological motifs. The phosphorylation site (His) is located in the middle of the domain, at the C terminus of a β-strand .

The PTS EIIA type 2 domain, which is found in the Mannitol class of PTS, has an average length of about 142 amino acids. It consists of an alternating β/α arrangement of five-stranded β-sheet and five α-helices, where the two last α helices forms an helical hairpin. The phosphorylation site (His) is located at the N terminus of the domain, at the topological switch-point of the structure, close to the subunit interface .

The PTS EIIA type 3 domain, which is found in the Lactose class of PTS, has an average length of about 100 amino acids. It is composed of three α-helices. The phosphorylation site (His) is located at the C terminus of the domain in the third α helix .

The PTS EIIA type 4 domain, which is found in the Mannose class of PTS, has an average length of about 130 amino acids. It consists of a single five-stranded mixed β sheet, flanked by helices on both sides. The phosphorylation site (His) is located at the end of the third β strand, in a shallow crevice lined with hydrophobic residues.

The PTS EIIA type 5 domain, which is found in the Sorbitol class of PTS, has an average length of about 110 amino acids. The phosphorylation site (His) is located at the N terminus of the domain.

EIIA-like domains similar to type 1 to 4 can be found in other kind of proteins, which are mainly transcriptional regulators . In these cases, the EIIA-like domain is found in association with other domains like the Sigma-54 interaction domain, the DeoR-type HTH domain, or the PTS regulation domain (transcriptional antiterminator). It may possess a regulatory function, through its phosphorylation activity, or act as a simple phosphoryl donor. Some proteins known to contains a EIIA-like domain are listed below:

Bacterial transcriptional regulatory proteins levR, nrtC, bglG.

Bacterial lactose permease lacS, a non-PTS transport system.

Bacterial PTS-dependent dihydroxyacetone kinase, phosphotransferase subunit dhaM.