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Gating modifier toxin interactions with ion channels and lipid bilayers: Is the trimolecular complex real?
Neuropharmacology. 2017 Dec; 127:32-45.N

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.'

Authors+Show Affiliations

Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia.Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia. Electronic address: s.henriques@uq.edu.au.Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia. Electronic address: c.schroeder@imb.uq.edu.au.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

28400258

Citation

Agwa, Akello J., et al. "Gating Modifier Toxin Interactions With Ion Channels and Lipid Bilayers: Is the Trimolecular Complex Real?" Neuropharmacology, vol. 127, 2017, pp. 32-45.
Agwa AJ, Henriques ST, Schroeder CI. Gating modifier toxin interactions with ion channels and lipid bilayers: Is the trimolecular complex real? Neuropharmacology. 2017;127:32-45.
Agwa, A. J., Henriques, S. T., & Schroeder, C. I. (2017). Gating modifier toxin interactions with ion channels and lipid bilayers: Is the trimolecular complex real? Neuropharmacology, 127, 32-45. https://doi.org/10.1016/j.neuropharm.2017.04.004
Agwa AJ, Henriques ST, Schroeder CI. Gating Modifier Toxin Interactions With Ion Channels and Lipid Bilayers: Is the Trimolecular Complex Real. Neuropharmacology. 2017;127:32-45. PubMed PMID: 28400258.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Gating modifier toxin interactions with ion channels and lipid bilayers: Is the trimolecular complex real? AU - Agwa,Akello J, AU - Henriques,Sónia T, AU - Schroeder,Christina I, Y1 - 2017/04/08/ PY - 2017/02/14/received PY - 2017/03/31/revised PY - 2017/04/05/accepted PY - 2017/4/13/pubmed PY - 2018/7/12/medline PY - 2017/4/13/entrez KW - Disulfide-rich peptides KW - Model membranes KW - Pain KW - Rational drug design KW - Sodium channel KW - Surface plasmon resonance SP - 32 EP - 45 JF - Neuropharmacology JO - Neuropharmacology VL - 127 N2 - 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.' SN - 1873-7064 UR - https://www.unboundmedicine.com/medline/citation/28400258/Gating_modifier_toxin_interactions_with_ion_channels_and_lipid_bilayers:_Is_the_trimolecular_complex_real L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028-3908(17)30141-7 DB - PRIME DP - Unbound Medicine ER -