The N-terminal half of the receptor domain of botulinum neurotoxin A binds to microdomains of the plasma membrane.

Research paper by Lucia L Muraro, Silvio S Tosatto, Lisa L Motterlini, Ornella O Rossetto, Cesare C Montecucco

Indexed on: 24 Jan '09Published on: 24 Jan '09Published in: Biochemical and Biophysical Research Communications


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.

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