Structural interactions of a voltage sensor toxin with lipid membranes.

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TitleStructural interactions of a voltage sensor toxin with lipid membranes.
Publication TypeJournal Article
Year of Publication2014
AuthorsMihailescu, M, Krepkiy, D, Milescu, M, Gawrisch, K, Swartz, KJ, White, S
JournalProc Natl Acad Sci U S A
Date Published2014 Dec 16
KeywordsAnimals, Cell Membrane, Ion Channels, Lipid Bilayers, Magnetic Resonance Spectroscopy, Multiprotein Complexes, Neutron Diffraction, Spectrometry, Fluorescence, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Spider Venoms

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.

Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID25453087
PubMed Central IDPMC4273406
Grant ListGM74637 / GM / NIGMS NIH HHS / United States
GM86685 / GM / NIGMS NIH HHS / United States
P01 GM086685 / GM / NIGMS NIH HHS / United States
R01 GM074637 / GM / NIGMS NIH HHS / United States
/ / Intramural NIH HHS / United States