Premium
Neutralisation of specific surface carboxylates speeds up translocation of botulinum neurotoxin type B enzymatic domain
Author(s) -
Pirazzini Marco,
Henke Tina,
Rossetto Ornella,
Mahrhold Stefan,
Krez Nadja,
Rummel Andreas,
Montecucco Cesare,
Binz Thomas
Publication year - 2013
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2013.10.010
Subject(s) - neurotoxin , membrane , chemistry , chromosomal translocation , enzyme , neutralization , protonation , biochemistry , glutamate receptor , mutant , biophysics , cytosol , neurotoxicity , amide , biology , ion , organic chemistry , toxicity , antibody , genetics , receptor , gene
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.