Molecular interaction of delta-conotoxins with voltage-gated sodium channels

Enrico Leipold, Alfred Hansel, Baldomero M Olivera, Heinrich Terlau, Stefan H Heinemann


Various neurotoxic peptides modulate voltage-gated sodium (Na(V)) channels and thereby affect cellular excitability. Delta-conotoxins from predatory cone snails slow down inactivation of Na(V) channels, but their interaction site and mechanism of channel modulation are unknown. Here, we show that delta-conotoxin SVIE from Conus striatus interacts with a conserved hydrophobic triad (YFV) in the domain-4 voltage sensor of Na(V) channels. This site overlaps with that of the scorpion alpha-toxin Lqh-2, but not with the alpha-like toxin Lqh-3 site. Delta-SVIE functionally competes with Lqh-2, but exhibits strong cooperativity with Lqh-3, presumably by synergistically trapping the voltage sensor in its "on" position.

Original languageEnglish
JournalFEBS Letters
Issue number18
Pages (from-to)3881-4
Number of pages4
Publication statusPublished - 18.07.2005


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