1.C.72 The Pertussis Toxin (PTX) Family
Pertussis toxin is an NAD-dependent ADP-ribosyltransferase. It catalyzes the ADP-ribosylation of a cysteine in the alpha subunit of heterotrimeric G proteins. In the absence of G proteins it also catalyzes the cleavage of NAD(+) into ADP-ribose and nicotinamide. It irreversibly uncouples the G-alpha GTP-binding proteins from their membrane receptors.
Pertussis toxin contains five different chains, S1-S5. They are organized into 2 functional subunits: A, composed of S1 (which is toxic) and B, containing S2, S3, S5, and two copies of S4 (B binds to the membrane receptors). Dimers of S2-S4 and S3-S4 are held together by S5. The x-ray structure has been solved to 2.9 Å resolution (Hazes et al., 1996; Stein et al., 1994).
Pertussis toxin subunits require the Sec-dependent general secretory pathway (TC #3.A.5) for export across the cytoplasmic membrane to the periplasm. The type IV secretion pathway (IVSP) system (TC #3.A.7) then exports it across the outer membrane. Finally, unlike most other IVSP substrates, the holotoxin autotranslocates itself across the host cytoplasmic membrane into the host cell (Gauthier et al., 2003). Thus it must form a channel. Complex B (S2S3(S4)2S5) binds the glycan receptors on the host cell surface and facilitates translocation of the toxic subunit (S1) across the membrane (Beddoe et al., 2010). Subunits S2 and S3 are related and may be distantly related to members of the Aerolysin Family (TC #1.C.4).
A homologue, ArtAB of Salmonella enterica (TC#1.C.72.2.1), shows sequence similarity with pertussis toxin A, but ArtB shows little similarity with the S2-55 subunits of pertussis toxin. It shows no conserved domains in the CDD. However, homologues of ArtB are found in many Salmonella strains including Typhi, and Paratyphi, in Yersinia pestis and Y. enterocolitica, in the subtilase cytotoxin of E. coli (TC# 1.C.72.3.1) and in hypothetical proteins of Bordetella species including B. pertussis.