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Proc Natl Acad Sci U S A. 2014 Dec 16;111(50):E5463-70. doi: 10.1073/pnas.1415324111. Epub 2014 Dec 1.

Structural interactions of a voltage sensor toxin with lipid membranes.

Author information

1
Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD 20850; National Institute of Standards and Technology Center for Neutron Research, National Institute of Standards and Technology, Gaithersburg, MD 20899;
2
Molecular Physiology and Biophysics Section, Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892;
3
Molecular Physiology and Biophysics Section, Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892; Biology Division, University of Missouri, Columbia, MO 65211;
4
Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892; and.
5
Molecular Physiology and Biophysics Section, Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892; swartzk@ninds.nih.gov Stephen.white@uci.edu.
6
Department of Physiology and Biophysics, University of California, Irvine, CA 92697 swartzk@ninds.nih.gov Stephen.white@uci.edu.

Abstract

Protein toxins from tarantula venom alter the activity of diverse ion channel proteins, including voltage, stretch, and ligand-activated cation channels. Although tarantula toxins have been shown to partition into membranes, and the membrane is thought to play an important role in their activity, the structural interactions between these toxins and lipid membranes are poorly understood. Here, we use solid-state NMR and neutron diffraction to investigate the interactions between a voltage sensor toxin (VSTx1) and lipid membranes, with the goal of localizing the toxin in the membrane and determining its influence on membrane structure. Our results demonstrate that VSTx1 localizes to the headgroup region of lipid membranes and produces a thinning of the bilayer. The toxin orients such that many basic residues are in the aqueous phase, all three Trp residues adopt interfacial positions, and several hydrophobic residues are within the membrane interior. One remarkable feature of this preferred orientation is that the surface of the toxin that mediates binding to voltage sensors is ideally positioned within the lipid bilayer to favor complex formation between the toxin and the voltage sensor.

KEYWORDS:

membrane structure; neutron diffraction; toxin–membrane interaction; voltage sensor toxin; voltage-activated ion channel

PMID:
25453087
PMCID:
PMC4273406
DOI:
10.1073/pnas.1415324111
[Indexed for MEDLINE]
Free PMC Article

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