Structure and hydration of membranes embedded with voltage-sensing domains.
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.
Krepkiy
Dmitriy
D
Molecular Physiology and Biophysics Section, Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.
Mihailescu
Mihaela
M
Freites
J Alfredo
JA
Schow
Eric V
EV
Worcester
David L
DL
Gawrisch
Klaus
K
Tobias
Douglas J
DJ
White
Stephen H
SH
Swartz
Kenton J
KJ
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
D019843:Archaeal Proteins; D008051:Lipid Bilayers; D008563:Membrane Lipids; D024642:Potassium Channels, Voltage-Gated; D014867:Water