Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 380, Issue 1, Pages 76-80Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2009.01.037
Keywords
Botulinum neurotoxin; Botulism; Sphingomyelin; PIP; Membrane binding
Categories
Funding
- Telethon [GGP06133]
- Fondazione Cariparo Progetto Physiopathology of the synapse: neurotransmitters, neurotoxins and novel therapies
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Botulinum neurotoxin type A (BoNT/A) is largely employed in human therapy because of its specific inhibition of peripheral cholinergic nerve terminals. BoNT/A binds to them rapidly and with high specificity via its receptor binding domain termed HC. Recent evidence indicate that BoNT/A interacts specifically with polysialogangliosides and with a luminal loop of the synaptic vesicle protein SV2 via the C-terminal half of HC. Here we show that the N-terminal half of HC binds to sphingomyelin-enriched membrane microdomains and that it has a defined interaction With phosphatidylinositol phosphates (PIP). We have identified a PIP binding site in this half of HC and we show how this interaction Could predispose BoNT/A for membrane insertion, which is the step subsequent to binding, in the four-steps route leading BoNT/A inside nerve terminals. (C) 2009 Elsevier Inc. All rights reserved.
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