tailieunhanh - Báo cáo khoa học: 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 botulinumtype A as a complex with a group of neurotoxin-associated proteins (NAPs) through polycis-tronic 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 protec-tion of the botulinum neurotoxin from proteolysis. . | ềFEBS Journal Hemagglutinin-33 of type A botulinum neurotoxin complex binds with synaptotagmin II Yu Zhou Sean Foss Paul Lindo Hemanta Sarkar and Bal Ram Singh Department of Chemistry and Biochemistry and the Botulinum Research Center University of Massachusetts Dartmouth MA USA Keywords botulinum neurotoxin Clostridium hemagglutinin synaptotagmin synaptosomes Correspondence B. R. Singh Department of Chemistry and Biochemistry and Botulinum Research Center University of Massachusetts Dartmouth 285 Old Westport Road North Dartmouth MA 02747 USA Fax 1 508 999 8451 Tel 1 508 999 8588 E-mail bsingh@ Received 23 November 2004 revised 18 February 2005 accepted 28 March 2005 doi 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 antibotulism therapeutic agents targeted to block the entry of botulinum neurotoxin into nerve cells. Botulinum neurotoxins BoNTs are among the most potent toxins known approximately 100 billion times more toxic than cyanide 1 . BoNTs are the causative agents of food-borne infant and wound botulism 2 . Because of its extreme toxicity BoNT is also considered a dreaded biological weapon 3 . .

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