Comparative membrane channel size and activity of botulinum neurotoxins A and E.
In an effort to compare the molecular basis of differential toxic activity of botulinum neurotoxin A (BoNT/A) and BoNT/E, we have analyzed their membrane channel activity by measuring calcein release from liposomes. Both BoNT/A and /E showed a same level of membrane channel activity that was specifically blocked by IgG specific to the neurotoxins. With the use of fluorescein-labeled dextran, we determined that the size of the channel is at least 24.2 A which is appropriate for the translocation of a protein of 50 kDa (the light chain of BoNT). These findings would suggest that the difference in the toxicity level of the two BoNT serotypes might reflect differences in either endopeptidase activity or their binding to receptor(s).
Parikh
Sweta
S
Botulinum Research Center, University of Massachusetts Dartmouth, 285 Old Westport Road, Dartmouth, MA, 02747, USA.
Singh
Bal Ram
BR
D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D001667:Binding, Competitive / Q000276:immunology; D001905:Botulinum Toxins / Q000737:chemistry* / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism / Q000633:toxicity*; D019274:Botulinum Toxins, Type A / Q000737:chemistry* / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism / Q000633:toxicity*; D002463:Cell Membrane Permeability / Q000502:physiology; D003014:Clostridium botulinum / Q000145:classification / Q000166:cytology / Q000502:physiology*; D005452:Fluoresceins / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D006801:Humans; D007473:Ion Channels / Q000737:chemistry* / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism / Q000633:toxicity; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism; D008970:Molecular Weight; D011487:Protein Conformation; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D011817:Rabbits
D000907:Antibodies, Bacterial; D005452:Fluoresceins; D007473:Ion Channels; D008081:Liposomes; D021122:Protein Subunits; D001905:Botulinum Toxins; D019274:Botulinum Toxins, Type A; C096326:botulinum toxin type E; C007740:fluorexon