QUATERNARY STRUCTURE OF BOTULINUM AND TETANUS NEUROTOXINS AS PROBED BY CHEMICAL CROSS-LINKING AND NATIVE GEL-ELECTROPHORESIS

Botulinum and tetanus neurotoxins are water-soluble proteins (mel. wt 150,000) produced by Clostridium botulinum and Clostridium tetani, res pectively. It is believed that these neurotoxins, once internalized vi a receptor-mediated endocytosis, form membrane channels in order to tr averse the endosomal membrane and enter the cytoplasm of the nerve ter minal. Investigation of the associative properties between neurotoxin molecules could yield an understanding of this channel formation. That is, an association between neurotoxin monomers could, result in an ol igomeric form of the neurotoxin necessary for assembly of a channel th rough the hydrophobic interior of the endosomal membrane, thereby allo wing passage of the neurotoxin or its active fragment through the resu lting pore. Based on the native gel electrophoresis and chemical cross -linking experiments, tetanus neurotoxin exists as a dimer and a trime r, type A botulinum neurotoxin exists as a dimer, trimer, and a larger species, type E botulinum neurotoxin exists as a monomer and dimer, a nd type B botulinum neurotoxin appears to exist as a dimer in aqueous solution. The results imply that quaternary structures of these neurot oxins may play an important role in their mode of action during neuron al poisoning.