Gating modifier toxin interactions with ion channels and lipid bilayers: Is the trimolecular complex real?

Agwa, Akello J., Henriques, Sónia T. and Schroeder, Christina I. (2017) Gating modifier toxin interactions with ion channels and lipid bilayers: Is the trimolecular complex real?. Neuropharmacology, 127 32-45. doi:10.1016/j.neuropharm.2017.04.004


Author Agwa, Akello J.
Henriques, Sónia T.
Schroeder, Christina I.
Title Gating modifier toxin interactions with ion channels and lipid bilayers: Is the trimolecular complex real?
Journal name Neuropharmacology   Check publisher's open access policy
ISSN 1873-7064
0028-3908
Publication date 2017-04-08
Year available 2017
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1016/j.neuropharm.2017.04.004
Open Access Status Not yet assessed
Volume 127
Start page 32
End page 45
Total pages 14
Place of publication Kidlington, Oxford United Kingdom
Publisher Pergamon Press
Language eng
Subject 3004 Pharmacology
2804 Cellular and Molecular Neuroscience
Abstract Spider peptide toxins have attracted attention because of their ability to target voltage-gated ion channels, which are involved in several pathologies including chronic pain and some cardiovascular conditions. A class of these peptides acts by modulating the gating mechanism of voltage-gated ion channels and are thus called gating modifier toxins (GMTs). In addition to their interactions with voltage-gated ion channels, some GMTs have affinity for lipid bilayers. This review discusses the potential importance of the cell membrane on the mode of action of GMTs. We propose that peptide–membrane interactions can anchor GMTs at the cell surface, thereby increasing GMT concentration in the vicinity of the channel binding site. We also propose that modulating peptide–membrane interactions might be useful for increasing the therapeutic potential of spider toxins. Furthermore, we explore the advantages and limitations of the methodologies currently used to examine peptide–membrane interactions. Although GMT–lipid membrane binding does not appear to be a requirement for the activity of all GMTs, it is an important feature, and future studies with GMTs should consider the trimolecular peptide–lipid membrane–channel complex. This article is part of the Special Issue entitled ‘Venom-derived Peptides as Pharmacological Tools.’
Keyword Disulfide-rich peptides
Model membranes
Pain
Rational drug design
Sodium channel
Surface plasmon resonance
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collections: HERDC Pre-Audit
Institute for Molecular Bioscience - Publications
 
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Created: Sat, 16 Dec 2017, 19:41:10 EST