ABSTRACT

Much of the early work on the botulinum toxins focused on characterizing the molecular structure, function, and pathogenic effects of type A toxin. The crystalline form of this toxin was found to have a molecular weight of around 900 kD and a 19S sedimentation constant [9]. However, the combined molecular weight of the constituent heavy and light chains of the purified neurotoxin was only 150-160 kD, with a corresponding sedimentation constant of only 7S. The large crystalline “progenitor toxin” form was subsequently shown to consist of the “derivative” 7S neurotoxin component along with two or more noncovalently linked, nontoxic accessory proteins. The nontoxic components of the progenitor toxin complex were later identified as hemagglutinin (HA) and nontoxic nonhemagglutinin (NTNH) proteins (reviewed in ref. [1]). The NTNH protein is synthesized by all

C. botulinum

serotypes

and is generally found in all neurotoxin complexes with sedimentation constants of 12S or greater. Only certain serotypes produce HA-containing progenitor toxins, however, and these multimeric complexes typically have sedimentation constants of 16S or higher. Type A toxins are synthesized in 900-kD (19S), 500-kD (16S), and 300-kD (12S) forms; toxins B, C, and D are produced in 500-kD (16S) or 300-kD (12S) forms; serotypes E and F synthesize only the 300-kD (12S) toxin; and toxin G is only synthesized in the 500-kD (16S) form [10]. However, various purification procedures can also be used to isolate the 7S neurotoxin with or without the associated nontoxic components of the larger multimeric complexes.