Hemagglutinin-33 of type A botulinum neurotoxin complex binds with synaptotagmin II.
Botulinum neurotoxin type A (BoNT/A), the most toxic substance known to mankind, is produced by Clostridium botulinum type A as a complex with a group of neurotoxin-associated proteins (NAPs) through polycistronic expression of a clustered group of genes. NAPs are known to protect BoNT against adverse environmental conditions and proteolytic digestion. Hemagglutinin-33 (Hn-33) is a 33 kDa subcomponent of NAPs that is resistant to protease digestion, a feature likely to be involved in the protection of the botulinum neurotoxin from proteolysis. However, it is not known whether Hn-33 plays any role other than the protection of BoNT. Using immunoaffinity column chromatography and pull-down assays, we have now discovered that Hn-33 binds to synaptotagmin II, the putative receptor of botulinum neurotoxin. This finding provides important information relevant to the design of novel anti-botulism therapeutic agents targeted to block the entry of botulinum neurotoxin into nerve cells.
Zhou
Yu
Y
Department of Chemistry and Biochemistry, and Botulinum Research Center, University of Massachusetts North Dartmouth, MA 02747, USA.
Foss
Sean
S
Lindo
Paul
P
Sarkar
Hemanta
H
Singh
Bal Ram
BR
D001426:Bacterial Proteins / Q000378:metabolism*; D001905:Botulinum Toxins; D019274:Botulinum Toxins, Type A / Q000378:metabolism*; D002846:Chromatography, Affinity; D003014:Clostridium botulinum / Q000378:metabolism*; D006388:Hemagglutinins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D050861:Synaptotagmin II
D001426:Bacterial Proteins; D006388:Hemagglutinins; D009419:Nerve Tissue Proteins; D050861:Synaptotagmin II; C118973:hemagglutinin 33 protein, Clostridium botulinum; D001905:Botulinum Toxins; D019274:Botulinum Toxins, Type A