Journal
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
Volume 1858, Issue 4, Pages 872-882Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbamem.2016.02.002
Keywords
Venom peptide; Toxin; Gating modifier; Pore blacker; Voltage-gated ion channel; Lipid binding; Phospholipid membrane; Surface plasmon resonance; Molecular dynamics simulations
Categories
Funding
- Australian National Health and Medical Research (NHMRC) [APP1080405, APP1071293, APP1026501, APP1034958, APP10/11114, DP130102153]
- Australian Government
Ask authors/readers for more resources
Many venom peptides are potent and selective inhibitors of voltage-gated ion channels, including channels that are validated therapeutic targets for treatment of a wide range of human diseases. However, the development of novel venom-peptide-based therapeutics requires an understanding of their mechanism of action. In the case of voltage-gated ion channels, venom peptides act either as pore blockers that bind to the extracellular side of the channel pore or gating modifiers that bind to one or more of the membrane-embedded voltage sensor domains. In the case of gating modifiers, it has been debated whether the peptide must partition into the membrane to reach its binding site.ln this study, we used surface plasmon resonance, fluorescence spectroscopy and molecular dynamics to directly compare the lipid-binding properties of two gating modifiers (mu-TRTX-Hd1a and ProTx-I) and two pore blockers (ShK and KIIIA). Only ProTx-I was found to bind to model membranes. Our results provide further evidence that the ability to insert into the lipid bilayer is not a requirement to be a gating modifier. In addition, we characterised the surface of ProTx-I that mediates its interaction with neutral and anionic phospholipid membranes and show that it preferentially interacts with anionic lipids. (C) 2016 Elsevier B.V. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available