Novel Ganglioside-mediated Entry of Botulinum Neurotoxin Serotype D into Neurons

Botulinum Neurotoxin Serotype C Associates with Dual Ganglioside Receptors to Facilitate Cell Entry

“…C, the indicated HCR (5 nM) was incubated in wells coated with GD3, GD2, or GD1b or uncoated. The plate was processed as described in B. HCR/D (10 nM) was included as a positive control for GD2 binding (27). These results indicate that ganglioside binding by the Sia-1 site requires a terminal galactose ring on the sugar backbone to bind efficiently.…”

Enhancing the Protective Immune Response against Botulism

“…Since W is conserved within the GBPs of BoNT serotypes A, B, E, F, G and tetanus toxin (17,20,(44)(45)(46)(47), we propose that this mutation can be introduced into each HCR serotype to generate a potentially less reactive but more potent vaccine. In addition, since BoNT/C and BoNT/D possess comparable aromatic residues within another ganglioside binding loop within the HCR (48,49), we propose that the respective W and F may be modified to A to reduce potential reactivity and enhance vaccine potency. The inadvertent hazard of retaining ganglioside binding was reported during the development of the cholera toxin B subunit in adjuvant development (50).…”

Unique Biological Activity of Botulinum D/C Mosaic Neurotoxin in Murine Species

“…2 and 7). Recent analyses based on the crystal structures of type C and D H C s have revealed the presence of ganglioside-binding sites in each BoNT (13,14,25). We investigated the role of ganglioside as the functional receptor for BoNT/C and D and the two mosaic BoNTs.…”

“…Meanwhile, for BoNT/C, gangliosides GD1b and GT1b have been identified as binding components (42). Although BoNT/D lacks the SXWY ganglioside-binding motif that is present in other BoNT serotypes, it has recently been reported that the toxin binds to b-series gangliosides (14).…”