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 voltage-gated calcium channel alpha-1 subunit. The most potent of these is known as omega-conotoxin GVIA from the species Conus geographus, a marine snail that has been responsible for a number of human fatalities. Using theoretical techniques we present a plausible binding model of the conotoxin to a loop region of the channel. Our model of the toxin binding region also contains a possible EF-hand motif and we suggest that this Ca2+ binding domain lies on the ion permeation pathway, a possible Ca2+ recruitment site.