Nishizawa, Kazuhisa
Atomistic Molecular Simulation of Gating Modifier Venom Peptides - Two Binding Modes and Effects of Lipid Structure
MECHANOSENSITIVITY AND MECHANOTRANSDUCTION, 4:167-190, 2011

GsMTx4 a gating modifier peptide obtained from tarantula venom has been a valuable tool for investigating the gating mechanisms of mechanosensitive channels GsMTx4 is thought to act at the channel/lipid interface by modifying the structure of the surrounding lipid molecules However the atomistic details of these actions are poorly understood Here the studies of GsMTx4 and related pep tide toxins that inhibit the voltage activation of various ion channels are reviewed with emphasis on the results of molecular dynamic (MD) simulation analyses Free energy profile analyses suggest that these toxins exhibit two modes of binding to lipid membrane namely the shallow mode and the deep mode These toxins favor the deep mode especially in membranes rich in saturated lipid acyl chains which make the headgroup layer tight It is hypothesized that in the case of HaTx the deep mode is the action mode while for GsMTx4 the two modes can explain the concentration dependent (biphasic) effect of GsMTx4 that has recently been reported The possibility that such toxins seek out specific types of lipid molecules is discussed Simulation results support the view that the channel/GsMTx4 (or HaTx)/lipids make a tertiary complex crucial to the effectiveness of the toxin and therefore binding of the toxin to channels occurs only in the presence of lipid molecules with appropriate structures

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