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Molecular interaction of δ‐conotoxins with voltage‐gated sodium channels
Author(s) -
Leipold Enrico,
Hansel Alfred,
Olivera Baldomero M.,
Terlau Heinrich,
Heinemann Stefan H.
Publication year - 2005
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2005.05.077
Subject(s) - sodium channel , conotoxin , chemistry , conus , biophysics , sodium , anatomy , biology , venom , biochemistry , organic chemistry
Various neurotoxic peptides modulate voltage‐gated sodium (Na V ) channels and thereby affect cellular excitability. δ‐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 δ‐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 α‐toxin Lqh‐2, but not with the α‐like toxin Lqh‐3 site. δ‐SVIE functionally competes with Lqh‐2, but exhibits strong cooperativity with Lqh‐3, presumably by synergistically trapping the voltage sensor in its “on” position.