期刊
FEBS LETTERS
卷 587, 期 23, 页码 3831-3836出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.febslet.2013.10.010
关键词
Botulinum neurotoxin; Translocation; pH sensor; Bafilomycin A1; Phrenic nerve hemidiaphragm toxicity test
资金
- Deutsche Forschungsgemeinschaft [BI 660/3-1]
- Bundesministerium fur Bildung und Forschung [FK031A212A]
- MIUR (Progetto PRIN)
- University of Padova
- Fondazione CARIPARO
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. (C) 2013 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.
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