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Publication : Identification of the synaptic vesicle glycoprotein 2 receptor binding site in botulinum neurotoxin A.

First Author  Strotmeier J Year  2014
Journal  FEBS Lett Volume  588
Issue  7 Pages  1087-93
PubMed ID  24583011 Mgi Jnum  J:207397
Mgi Id  MGI:5556328 Doi  10.1016/j.febslet.2014.02.034
Citation  Strotmeier J, et al. (2014) Identification of the synaptic vesicle glycoprotein 2 receptor binding site in botulinum neurotoxin A. FEBS Lett 588(7):1087-93
abstractText  Botulinum neurotoxins (BoNTs) inhibit neurotransmitter release by hydrolysing SNARE proteins. The most important serotype BoNT/A employs the synaptic vesicle glycoprotein 2 (SV2) isoforms A-C as neuronal receptors. Here, we identified their binding site by blocking SV2 interaction using monoclonal antibodies with characterised epitopes within the cell binding domain (HC). The site is located on the backside of the conserved ganglioside binding pocket at the interface of the HCC and HCN subdomains. The dimension of the binding pocket was characterised in detail by site directed mutagenesis allowing the development of potent inhibitors as well as modifying receptor binding properties.
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