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Open AccessArticle

Effect of Gating Modifier Toxins on Membrane Thickness: Implications for Toxin Effect on Gramicidin and Mechanosensitive Channels

Research School of Biology, Australian National University, Canberra, ACT 0200, Australia
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Toxins 2013, 5(2), 456-471; https://doi.org/10.3390/toxins5020456
Received: 6 January 2013 / Revised: 18 February 2013 / Accepted: 18 February 2013 / Published: 22 February 2013
Various gating modifier toxins partition into membranes and interfere with the gating mechanisms of biological ion channels. For example, GsMTx4 potentiates gramicidin and several bacterial mechanosensitive channels whose gating kinetics are sensitive to mechanical properties of the membrane, whereas binding of HpTx2 shifts the voltage-activity curve of the voltage-gated potassium channel Kv4.2 to the right. The detailed process by which the toxin partitions into membranes has been difficult to probe using molecular dynamics due to the limited time scale accessible. Here we develop a protocol that allows the spontaneous assembly of a polypeptide toxin into membranes in atomistic molecular dynamics simulations of tens of nanoseconds. The protocol is applied to GsMTx4 and HpTx2. Both toxins, released in water at the start of the simulation, spontaneously bind into the lipid bilayer within 50 ns, with their hydrophobic patch penetrated into the bilayer beyond the phosphate groups of the lipids. It is found that the bilayer is about 2 Å thinner upon the binding of a GsMTx4 monomer. Such a thinning effect of GsMTx4 on membranes may explain its potentiation effect on gramicidin and mechanosensitive channels. View Full-Text
Keywords: membrane; lipid bilayer; gating modifier toxin; molecular dynamics membrane; lipid bilayer; gating modifier toxin; molecular dynamics
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Chen, R.; Chung, S.-H. Effect of Gating Modifier Toxins on Membrane Thickness: Implications for Toxin Effect on Gramicidin and Mechanosensitive Channels. Toxins 2013, 5, 456-471.

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