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Hemagglutinin-33 of type A botulinum neurotoxin complex binds with synaptotagmin II.

Zhou Y, Foss S, Lindo P, Sarkar H, Singh BR

Department of Chemistry and Biochemistry, and Botulinum Research Center, University of Massachusetts North Dartmouth, MA 02747, USA.

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.

Published 9 June 2005 in FEBS J, 272(11): 2717-26.
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