A MOLECULAR MECHANISM FOR TOXIN BLOCK IN N-TYPE CALCIUM CHANNELS

A series of highly toxic snail venoms, the omega-conotoxins, have been shown to bind selectively, and often irreversibly to the N-type volta ge-gated calcium channel alpha-1 subunit, The most potent of these is known as omega-conotoxin GVIA from the species Conus geographus, a mar ine snail that has been responsible for a number of human fatalities. Using theoretical techniques we present a plausible binding model of t he conotoxin to a loop region of the channel, Our model of the toxin b inding region also contains a possible EF-hand motif and we suggest th at this Ca2+ binding domain lies on the ion permeation pathway, a poss ible Ca2+ recruitment site.