Identification of the synaptic vesicle glycoprotein 2 receptor binding site in botulinum neurotoxin A
Copyright policy )Identification of the synaptic vesicle glycoprotein 2 receptor binding site in botulinum neurotoxin A
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.
- UNIVERSITY OF CALIFORNIA-IRVINE
- Medizinische Hochschule Hannover, Institut für Toxikologie Germany
- University of California, San Francisco United States
- University of California System United States
- Hochschule Hannover Germany
Monoclonal antibody, 570, Biochemistry & Molecular Biology, Protein receptor binding site, Botulinum Toxins, Neurotoxins, Neural Conduction, 610, Nerve Tissue Proteins, Inbred C57BL, Type A, Neutralisation, Medicinal and Biomolecular Chemistry, Inhibitory Concentration 50, Mice, Biodefense, Site-Directed, Animals, Humans, Protein Interaction Domains and Motifs, Botulinum Toxins, Type A, Evolutionary Biology, Botulinum neurotoxin A, SV2, Binding Sites, Membrane Glycoproteins, Neurosciences, Biological Sciences, Foodborne Illness, Mice, Inbred C57BL, Phrenic Nerve, Emerging Infectious Diseases, Infectious Diseases, Amino Acid Substitution, 5.1 Pharmaceuticals, Mutagenesis, Biochemistry and cell biology, Mutagenesis, Site-Directed, Biochemistry and Cell Biology, Generic health relevance, Protein Binding
Monoclonal antibody, 570, Biochemistry & Molecular Biology, Protein receptor binding site, Botulinum Toxins, Neurotoxins, Neural Conduction, 610, Nerve Tissue Proteins, Inbred C57BL, Type A, Neutralisation, Medicinal and Biomolecular Chemistry, Inhibitory Concentration 50, Mice, Biodefense, Site-Directed, Animals, Humans, Protein Interaction Domains and Motifs, Botulinum Toxins, Type A, Evolutionary Biology, Botulinum neurotoxin A, SV2, Binding Sites, Membrane Glycoproteins, Neurosciences, Biological Sciences, Foodborne Illness, Mice, Inbred C57BL, Phrenic Nerve, Emerging Infectious Diseases, Infectious Diseases, Amino Acid Substitution, 5.1 Pharmaceuticals, Mutagenesis, Biochemistry and cell biology, Mutagenesis, Site-Directed, Biochemistry and Cell Biology, Generic health relevance, Protein Binding
selected citations These citations are derived from selected sources.This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).40 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!