Structure and hydration of membranes embedded with voltage-sensing domains.

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TitleStructure and hydration of membranes embedded with voltage-sensing domains.
Publication TypeJournal Article
Year of Publication2009
AuthorsKrepkiy, D, Mihailescu, M, J Freites, A, Schow, EV, Worcester, DL, Gawrisch, K, Tobias, DJ, White, SH, Swartz, KJ
Date Published2009 Nov 26
KeywordsArchaeal Proteins, Circular Dichroism, Lipid Bilayers, Membrane Lipids, Membrane Potentials, Models, Molecular, Molecular Dynamics Simulation, Neutron Diffraction, Nuclear Magnetic Resonance, Biomolecular, Potassium Channels, Voltage-Gated, Protein Structure, Tertiary, Spectrometry, Fluorescence, Water

Despite the growing number of atomic-resolution membrane protein structures, direct structural information about proteins in their native membrane environment is scarce. This problem is particularly relevant in the case of the highly charged S1-S4 voltage-sensing domains responsible for nerve impulses, where interactions with the lipid bilayer are critical for the function of voltage-activated ion channels. Here we use neutron diffraction, solid-state nuclear magnetic resonance (NMR) spectroscopy and molecular dynamics simulations to investigate the structure and hydration of bilayer membranes containing S1-S4 voltage-sensing domains. Our results show that voltage sensors adopt transmembrane orientations and cause a modest reshaping of the surrounding lipid bilayer, and that water molecules intimately interact with the protein within the membrane. These structural findings indicate that voltage sensors have evolved to interact with the lipid membrane while keeping energetic and structural perturbations to a minimum, and that water penetrates the membrane, to hydrate charged residues and shape the transmembrane electric field.

Alternate JournalNature
PubMed ID19940918
PubMed Central IDPMC2784928
Grant ListGM74737 / 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
R01 RR014812 / RR / NCRR NIH HHS / United States
ZIA NS002945-13 / / Intramural NIH HHS / United States