Molecular interaction of delta-conotoxins with voltage-gated sodium channels.
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.
Institute of Molecular Cell Biology, Research Unit Molecular and Cellular Biophysics, Friedrich Schiller University Jena, Drackendorfer Strasse 1, D-07747 Jena, Germany.
Enrico
E
Leipold
Alfred
A
Hansel
Baldomero M
BM
Olivera
Heinrich
H
Terlau
Stefan H
SH
Heinemann
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D002460:Cell Line; D020916:Conotoxins / Q000378:metabolism*; D003545:Cysteine / Q000737:chemistry; D004594:Electrophysiology; D006801:Humans; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000378:metabolism; D009498:Neurotoxins / Q000737:chemistry; D011485:Protein Binding; D051381:Rats; D012604:Scorpion Venoms / Q000737:chemistry / Q000378:metabolism; D012605:Scorpions; D017386:Sequence Homology, Amino Acid; D015222:Sodium Channels / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection
D020916:Conotoxins; C114938:Lqh II toxin; C114939:Lqh III toxin; D009124:Muscle Proteins; D009498:Neurotoxins; C466180:Scn4a protein, rat; D012604:Scorpion Venoms; D015222:Sodium Channels; C503212:delta-conotoxin SVIA, Conus striatus; D003545:Cysteine