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Identification of the synaptic vesicle glycoprotein 2 receptor binding site in botulinum neurotoxin A
Author(s) -
Strotmeier Jasmin,
Mahrhold Stefan,
Krez Nadja,
Janzen Constantin,
Lou Jianlong,
Marks James D.,
Binz Thomas,
Rummel Andreas
Publication year - 2014
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2014.02.034
Subject(s) - synaptic vesicle , binding site , chemistry , synaptotagmin 1 , receptor , biochemistry , neurotoxin , stx1a , gene isoform , clostridium botulinum , binding domain , mutagenesis , biology , microbiology and biotechnology , vesicle , toxin , mutation , membrane , gene
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 (H C ). The site is located on the backside of the conserved ganglioside binding pocket at the interface of the H CC and H CN 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.