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 (mol. wt 150,000) produced by Clostridium botulinum and Clostridium tetani, respectively. It is believed that these neurotoxins, once internalized via receptor-mediated endocytosis, form membrane channels in order to traverse the endosomal membrane and enter the cytoplasm of the nerve terminal. 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 oligomeric form of the neurotoxin necessary for assembly of a channel through the hydrophobic interior of the endosomal membrane, thereby allowing passage of the neurotoxin or its active fragment through the resulting pore. Based on the native gel electrophoresis and chemical cross-linking experiments, tetanus neurotoxin exists as a dimer and a trimer, type A botulinum neurotoxin exists as a dimer, trimer, and a larger species, type E botulinum neurotoxin exists as a monomer and dimer, and type B botulinum neurotoxin appears to exist as a dimer in aqueous solution. The results imply that quaternary structures of these neurotoxins may play an important role in their mode of action during neuronal poisoning.
Ledoux
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Department of Chemistry, University of Massachusetts Dartmouth 02747.
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D000596:Amino Acids / Q000032:analysis; D001905:Botulinum Toxins / Q000737:chemistry* / Q000378:metabolism; D003014:Clostridium botulinum / Q000378:metabolism; D003017:Clostridium tetani / Q000378:metabolism; D003432:Cross-Linking Reagents / Q000737:chemistry; D004492:Edetic Acid / Q000737:chemistry; D004591:Electrophoresis, Polyacrylamide Gel; D006863:Hydrogen-Ion Concentration; D008970:Molecular Weight; D009498:Neurotoxins / Q000737:chemistry* / Q000378:metabolism; D011108:Polymers; D011487:Protein Conformation; D013744:Tetanus Toxin / Q000737:chemistry* / Q000378:metabolism
D000596:Amino Acids; D003432:Cross-Linking Reagents; D009498:Neurotoxins; D011108:Polymers; D013744:Tetanus Toxin; D004492:Edetic Acid; D001905:Botulinum Toxins