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

Akello J Agwa, Sónia T Henriques, Christina I Schroeder

Research output: Contribution to journalReview articlepeer-review

14 Citations (SciVal)


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.'

Original languageEnglish
Pages (from-to)32-45
Number of pages14
Early online date8 Apr 2017
Publication statusPublished - Dec 2017

Bibliographical note

Copyright © 2017 Elsevier Ltd. All rights reserved.


  • Animals
  • Binding Sites/drug effects
  • Cell Membrane/drug effects
  • Ion Channel Gating/drug effects
  • Lipid Bilayers/metabolism
  • Peptides/pharmacology
  • Spider Venoms/pharmacology


Dive into the research topics of 'Gating modifier toxin interactions with ion channels and lipid bilayers: Is the trimolecular complex real?'. Together they form a unique fingerprint.

Cite this