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.

Originalsprache	Englisch
Zeitschrift	FEBS Letters
Jahrgang	579
Ausgabenummer	18
Seiten (von - bis)	3881-4
Seitenumfang	4
ISSN	0014-5793
DOIs	https://doi.org/10.1016/j.febslet.2005.05.077
Publikationsstatus	Veröffentlicht - 18.07.2005

UN SDGs

Dieser Output leistet einen Beitrag zu folgendem(n) Ziel(en) für nachhaltige Entwicklung

SDG 3 – Gesundheit und Wohlergehen

Dokumente

10.1016/j.febslet.2005.05.077

Zitieren

@article{eb2b8e27592542f2b62e13e2bb6acaef,

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\}",

year = "2005",

month = jul,

day = "18",

doi = "10.1016/j.febslet.2005.05.077",

language = "English",

volume = "579",

pages = "3881--4",

journal = "FEBS Letters",

issn = "0014-5793",

publisher = "John Wiley and Sons Inc",

number = "18",

}

TY - JOUR

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

UN SDGs

Dokumente

Fingerprint

Zitieren