Discovery of a novel enzymatic cleavage site for botulinum neurotoxin F5. FEBS Lett

Centers for Disease Control and Prevention, National Center for Environmental Health, Division of Laboratory Sciences, 4770 Buford Hwy, NE, Atlanta, GA 30341, USA.
FEBS letters (Impact Factor: 3.17). 12/2011; 586(2):109-15. DOI: 10.1016/j.febslet.2011.11.033
Source: PubMed


Botulinum neurotoxins (BoNTs) cause botulism by cleaving proteins necessary for nerve transmission. There are seven serotypes of BoNT, A-G, characterized by their response to antisera. Many serotypes are further distinguished into differing subtypes based on amino acid sequence, some of which result in functional differences. Our laboratory previously reported that all tested subtypes within each serotype have the same site of enzymatic activity. Recently, three new subtypes of BoNT/F; /F3, /F4, and /F5, were reported. Here, we report that BoNT/F5 cleaves substrate synaptobrevin-2 in a different location than the other BoNT/F subtypes, between (54)L and (55)E. This is the first report of cleavage of synaptobrevin-2 in this location.

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    • "Because the amino acid variance can result in antigenic differences, it is possible that amino acid variance would also result in enzymatic differences in terms of substrate and cleavage location. Our experiments determined that multiple BoNT/A, /B, /E, and /F subtypes, with the exception of BoNT/F5 (Kalb et al., 2012a), cleave their respective substrates at identical sites, despite having large genetic differences in their neurotoxins. These data imply that the non-commercial subtypes of BoNT/A, /B, /E, and /F have the ability to cleave the natural, in vivo substrate, SNAP-25 or VAMP-2, in the same location as the commercial subtypes of BoNT/A, /B, /E, and /F. "
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