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Updated: May 6, 2026

A High-throughput-compatible FRET-based Platform for Identification and Characterization of Botulinum Neurotoxin Light Chain Modulators
Published on: December 27, 2013
Neutralisation of specific surface carboxylates speeds up translocation of botulinum neurotoxin type B enzymatic
Marco Pirazzini1, Tina Henke, Ornella Rossetto
1Dipartimento di Scienze Biomediche and Istituto CNR di Neuroscienze, Università di Padova, Viale Ugo Bassi 58/B, 35131 Padova, Italy.
Abstract:
Botulinum neurotoxins translocate their enzymatic domain across vesicular membranes. The molecular triggers of this process are unknown. Here, we tested the possibility that this is elicited by protonation of conserved surface carboxylates. Glutamate-48, glutamate-653 and aspartate-877 were identified as possible candidates and changed into amide. This triple mutant showed increased neurotoxicity due to faster cytosolic delivery of the enzymatic domain; membrane translocation could take place at less acidic pH. Thus, neutralisation of specific negative surface charges facilitates membrane contact permitting a faster initiation of the toxin membrane insertion.
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