Structural highlights
Publication Abstract from PubMedBotulinum neurotoxins (BoNTs) and tetanus neurotoxin (TeNT) are the causative agents of the paralytic diseases botulism and tetanus, respectively. The potency of the clostridial neurotoxins (CNTs) relies primarily on their highly specific binding to nerve terminals and cleavage of SNARE (soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor) proteins. While individual CNTs utilize distinct proteins for entry, they share common ganglioside co-receptors. Here we report the crystal structure of the BoNT/F receptor binding domain in complex with the sugar moiety of ganglioside GD1a. GD1a binds in a shallow groove formed by a conserved peptide motif E...H...SXWY...G, with additional stabilizing interactions provided by two arginine residues. Comparative analysis of BoNT/F with other CNTs revealed several differences in the interactions of each toxin with ganglioside. Notably, exchange of BoNT/F His1241 with the corresponding lysine residue of BoNT/E resulted in increased affinity towards GD1a and conferred the ability to bind ganglioside GM1a. Conversely, BoNT/E was not able to bind GM1a, demonstrating a discreet mechanism of ganglioside recognition. These findings provide a structural basis for ganglioside binding among the clostridial neurotoxins and show that individual toxins utilize unique ganglioside recognition strategies. Unique ganglioside recognition strategies for clostridial neurotoxins.,Benson MA, Fu Z, Kim JJ, Baldwin MR J Biol Chem. 2011 Aug 17. PMID:21849494[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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