Journal
FEBS LETTERS
Volume 586, Issue 4, Pages 310-313Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.febslet.2011.12.037
Keywords
Botulinum neurotoxin B; BoNT/G; Protein receptor; Human synaptotagmin-II; RimabotulinumtoxinB
Funding
- Deutsche Forschungsgemeinschaft [BI 660/2-1, GSC108]
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Botulinum neurotoxins (BoNTs) inhibit neurotransmitter release by hydrolysing SNARE proteins essential for exocytosis. The synaptic vesicle protein synaptotagmin-II of rat and mouse acts as neuronal high affinity receptor for BoNT/B and BoNT/G. Here, we show that human synaptotagmin-II is not a high affinity receptor for BoNT/B and G due to a phenylalanine to leucine mutation in its luminal domain present only in humans and chimpanzees. It eliminates one of three major interactions between synaptotagmin-II and BoNT/B and hereby explains the disparity in potency of BoNT/B in humans and mice as well as the 40-fold higher dosage of rimabotulinumtoxinB versus onabotulinumtoxinA. Structured summary of protein interactions: rSyt-II binds to BoNT/G by pull down (View Interaction: 1, 2) rSyt-II binds to BoNT/B by pull down (View Interaction: 1, 2) (C) 2012 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.
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