title: Diverse binding modes, same goal: The receptor recognition mechanism of botulinum neurotoxin.
abstract: Botulinum neurotoxins (BoNTs) are among the most deadly toxins known. They act rapidly in a highly specific manner to block neurotransmitter release by cleaving the soluble N-ethylmaleimide sensitive factor attachment protein receptor (SNARE) complex at neuromuscular junctions. The extreme toxicity of BoNTs relies predominantly on their neurotropism that is accomplished by recognition of two host receptors, a polysialo-ganglioside and in the majority of cases a synaptic vesicle protein, through their receptor-binding domains. Two proteins, synaptotagmin and synaptic vesicle glycoprotein 2, have been identified as the receptors for various serotypes of BoNTs. Here, we review recent breakthroughs in the structural studies of BoNT-protein receptor recognitions that highlight a range of diverse mechanisms by which BoNTs manipulate host neuronal proteins for highly specific uptake at neuromuscular junctions.
authors.affiliation: Department of Physiology and Biophysics, University of California, Irvine, CA 92697, USA.
authors.forename: Kwok-Ho
authors.initials: KH
authors.lastname: Lam
authors.affiliation: Department of Physiology and Biophysics, University of California, Irvine, CA 92697, USA.
authors.forename: Guorui
authors.initials: G
authors.lastname: Yao
authors.affiliation: Department of Physiology and Biophysics, University of California, Irvine, CA 92697, USA. Electronic address: r.jin@uci.edu.
authors.forename: Rongsheng
authors.initials: R
authors.lastname: Jin
mesh_terms: D001665:Binding Sites; D001905:Botulinum Toxins / Q000737:chemistry* / Q000648:ultrastructure*; D003198:Computer Simulation; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000648:ultrastructure*; D008956:Models, Chemical; D008958:Models, Molecular; D008959:Models, Neurological; D009498:Neurotoxins / Q000737:chemistry*; D011485:Protein Binding; D013569:Synapses / Q000737:chemistry* / Q000648:ultrastructure
chemical_list: D008562:Membrane Glycoproteins; D009498:Neurotoxins; D001905:Botulinum Toxins
keywords: Botulinum neurotoxin; Botulism; Host-pathogen recognition; Protein complex; Synaptic vesicle glycoprotein 2; Synaptotagmin