Structure and orientation of a voltage-sensor toxin in lipid membranes.

Biophysical Journal
Hyun Ho JungJae Il Kim

Abstract

Amphipathic protein toxins from tarantula venom inhibit voltage-activated potassium (Kv) channels by binding to a critical helix-turn-helix motif termed the voltage sensor paddle. Although these toxins partition into membranes to bind the paddle motif, their structure and orientation within the membrane are unknown. We investigated the interaction of a tarantula toxin named SGTx with membranes using both fluorescence and NMR spectroscopy. Depth-dependent fluorescence-quenching experiments with brominated lipids suggest that Trp30 in SGTx is positioned approximately 9 A from the center of the bilayer. NMR spectra reveal that the inhibitor cystine knot structure of the toxin does not radically change upon membrane partitioning. Transferred cross-saturation NMR experiments indicate that the toxin's hydrophobic protrusion contacts the hydrophobic core of the membrane, whereas most surrounding polar residues remain at interfacial regions of the bilayer. The inferred orientation of the toxin reveals a twofold symmetry in the arrangement of basic and hydrophobic residues, a feature that is conserved among tarantula toxins. These results have important implications for regions of the toxin involved in recognizing membranes and voltage-...Continue Reading

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Citations

Jan 30, 2013·The Journal of General Physiology·Mirela MilescuKenton J Swartz
Dec 3, 2014·Proceedings of the National Academy of Sciences of the United States of America·Mihaela MihailescuStephen White
Sep 19, 2015·Scientific Reports·Shin-ichiro OzawaMasanori Osawa
Dec 19, 2012·Toxicon : Official Journal of the International Society on Toxinology·Huai TaoSongping Liang
Nov 5, 2016·Toxicon : Official Journal of the International Society on Toxinology·Huai TaoSongping Liang
Jan 12, 2017·Biophysical Journal·Radhakrishnan GnanasambandamThomas M Suchyna
Apr 29, 2018·The Journal of Biological Chemistry·Akello J AgwaChristina I Schroeder
Jun 6, 2020·Frontiers in Pharmacology·Kenny M Van TheemscheAlain J Labro

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