Chemistry of Cholera Toxin: The Subunit Structure

Abstract
The toxin of Vibrio cholerae was separated into two subunits by gel filtration on Sephadex G-75 in 5% formic acid. The subunits were designated A and B. Amino acid analysis indicated that subunit B corresponded to choleragenoid. Renatured subunit B was found to be antigenically identical to the whole molecule, whereas renatured subunit A was not. On reduction and S-carboxymethylation with [2-14C] iodoacetate in 8 M urea, subunit A separated into two polypeptides of unequal sizes, A1 and A2, with equal amounts of radioactivity. Subunit B, on the other hand, remained a single molecular species. Molecular weights of the polypeptides A1, A2, and B were estimated by polyacrylamide gel electrophoresis in sodium dodecyl sulfate-urea buffer, in conjunction with amino acid analysis, to be 20,000, 7,500, and 9,500 daltons, respectively. The carboxyl terminal sequence of subunit B was found to be -Met-Ala-Asn, After treatment of toxin with cyanogen bromide, the peptide Ala-Asn could be isolated and quantitated. From this data the number of B polypeptides in a molecule of toxin was estimated as six.