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

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

doi:10.1016/j.febslet.2005.05.077

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

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

Abstract

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 language	English
Journal	FEBS Letters
Volume	579
Issue number	18
Pages (from-to)	3881-4
Number of pages	4
ISSN	0014-5793
DOIs	https://doi.org/10.1016/j.febslet.2005.05.077
Publication status	Published - 18.07.2005

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title = "Molecular interaction of delta-conotoxins with voltage-gated sodium channels",

abstract = "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.",

author = "Enrico Leipold and Alfred Hansel and Olivera, {Baldomero M} and Heinrich Terlau and Heinemann, {Stefan H}",

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T1 - Molecular interaction of delta-conotoxins with voltage-gated sodium channels

AU - Leipold, Enrico

AU - Hansel, Alfred

AU - Olivera, Baldomero M

AU - Terlau, Heinrich

AU - Heinemann, Stefan H

PY - 2005/7/18

Y1 - 2005/7/18

N2 - 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.

AB - 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.

U2 - 10.1016/j.febslet.2005.05.077

DO - 10.1016/j.febslet.2005.05.077

M3 - Journal articles

C2 - 15990094

SN - 0014-5793

VL - 579

SP - 3881

EP - 3884

JO - FEBS Letters

JF - FEBS Letters

IS - 18

ER -

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

Abstract

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