Showing papers by "Thomas Binz published in 2003"
TL;DR: It is determined by mass spectroscopy studies that the HC‐fragment of botulinum neurotoxins A and B bind only one molecule of ganglioside GT1b, providing valuable information for the rational design of potent botulinu neurotoxin binding inhibitors.
Abstract: Tetanus and botulinum neurotoxins selectively invade neurons following binding to complex gangliosides Recent biochemical experiments demonstrate that two ganglioside binding sites within the tetanus neurotoxin HC-fragment, originally identified in crystallographic studies to bind lactose or sialic acid, are required for productive binding to target cells Here, we determine by mass spectroscopy studies that the HC-fragment of botulinum neurotoxins A and B bind only one molecule of ganglioside GT1b Mutations made in the presumed ganglioside binding site of botulinum neurotoxin A and B abolished the formation of these HC-fragment/ganglioside complexes, and drastically diminished binding to neuronal membranes and isolated GT1b Furthermore, correspondingly mutated full-length neurotoxins exhibit significantly reduced neurotoxicity, thus identifying a single ganglioside binding site within the carboxyl-terminal half of the HC-fragment of botulinum neurotoxins A and B These binding cavities are defined by the conserved peptide motif HSXWYG The roles of tyrosine and histidine in botulinum neurotoxins A and B in ganglioside binding differ from those in the analogous tetanus neurotoxin lactose site Hence, these findings provide valuable information for the rational design of potent botulinum neurotoxin binding inhibitors
257 citations
TL;DR: These data provide the first biochemical evidence that two carbohydrate interaction sites participate in the binding and uptake process of tetanus neurotoxin, via its carboxyl-terminal H(C)-fragment.
133 citations