title: Structure and hydration of membranes embedded with voltage-sensing domains.
abstract: 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.
authors: Molecular Physiology and Biophysics Section, Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors: Dmitriy
authors: D
authors: Krepkiy
authors: Mihaela
authors: M
authors: Mihailescu
authors: J Alfredo
authors: JA
authors: Freites
authors: Eric V
authors: EV
authors: Schow
authors: David L
authors: DL
authors: Worcester
authors: Klaus
authors: K
authors: Gawrisch
authors: Douglas J
authors: DJ
authors: Tobias
authors: Stephen H
authors: SH
authors: White
authors: Kenton J
authors: KJ
authors: Swartz
mesh_terms: D019843:Archaeal Proteins / Q000737:chemistry / Q000378:metabolism; D002942:Circular Dichroism; D008051:Lipid Bilayers / Q000737:chemistry* / Q000378:metabolism*; D008563:Membrane Lipids / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D008564:Membrane Potentials; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D033363:Neutron Diffraction; D019906:Nuclear Magnetic Resonance, Biomolecular; D024642:Potassium Channels, Voltage-Gated / Q000737:chemistry* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D013050:Spectrometry, Fluorescence; D014867:Water / Q000032:analysis* / Q000378:metabolism
chemical_list: D019843:Archaeal Proteins; D008051:Lipid Bilayers; D008563:Membrane Lipids; D024642:Potassium Channels, Voltage-Gated; D014867:Water