Structure and function of Clostridium botulinum progenitor toxin

Clostridium botulinum strains produce seven immunologically distinct neurotoxins (NTX), type A to G. The NTXs associate with nontoxic components in cultures, and become large complexes with three forms (12S, 16S, and 19S) designated progenitor toxins. The 12S toxin consists of a NTX and a nontoxic component having no hemagglutinin (HA) activity (described here as non-toxic non-HA, NTNH), and the 16S and 19S toxins are formed by conjugation of the 12S toxin with HA. Based on the genetic- and protein chemical-analyses of the progenitor toxins it became clear that 1) the HA consists of four subcomponents namely HA1 (Mr. 33 ~ 35 kDa), HA2 (15 ~ 17 kDa), HA3a (19 ~ 23 kDa), and HA3b (52 ~ 53 kDa), 2) the genes coding for NTX (ntx), NTNH (ntnh), and HA (ha) occur as a cluster; ha lies just upstream of ntnh, and ntx lies just downstream of ntnh, 3) ha is in the opposite orientation from that of ntnh and ntx, 4) ha consists of three ORFs (ha1, ha2, and ha3), 5) the gene product (70 kDa) of ha3 is split into HA3a and HA3b after translation, 6) HA3a is cleaved at several different sites of its N-terminal region to form proteins with slightly different Mrs, 7) the 19S toxin is a dimer of 16S toxin crosslinked by HA1, 8) The NTNHs of type A to D 12S toxins have a cleavage(s) on their N-terminal regions. It also became clear that the HA plays an important role when the 16S (and 19S) toxin is absorbed from the small intestine.