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VAMP/synaptobrevin cleavage by tetanus and botulinum neurotoxins is strongly enhanced by acidic liposomes
Author(s) -
Caccin Paola,
Rossetto Ornella,
Rigoni Michela,
Johnson Eric,
Schiavo Giampietro,
Montecucco Cesare
Publication year - 2003
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/s0014-5793(03)00365-x
Subject(s) - synaptic vesicle , chemistry , synaptobrevin , liposome , metalloproteinase , synaptotagmin 1 , cleavage (geology) , vesicle , biochemistry , peptide , endopeptidase , biophysics , microbiology and biotechnology , membrane , enzyme , biology , paleontology , fracture (geology)
Tetanus and botulinum neurotoxins (TeNT and BoNTs) block neuroexocytosis via specific cleavage and inactivation of SNARE proteins. Such activity is exerted by the N‐terminal 50 kDa light chain (L) domain, which is a zinc‐dependent endopeptidase. TeNT, BoNT/B, /D, /F and /G cleave vesicle associated membrane protein (VAMP), a protein of the neurotransmitter‐containing small synaptic vesicles, at different single peptide bonds. Since the proteolytic activity of these metalloproteases is higher on native VAMP inserted in synaptic vesicles than on recombinant VAMP, we have investigated the influence of liposomes of different lipid composition on this activity. We found that the rate of VAMP cleavage with all neurotoxins tested here is strongly enhanced by negatively charged lipid mixtures. This effect is at least partially due to the binding of the metalloprotease to the lipid membranes, with electrostatic interactions playing an important role.