title: Probing the interaction of the potassium channel modulating KCNE1 in lipid bilayers via solid-state NMR spectroscopy.
abstract: KCNE1 is known to modulate the voltage-gated potassium channel α subunit KCNQ1 to generate slowly activating potassium currents. This potassium channel is essential for the cardiac action potential that mediates a heartbeat as well as the potassium ion homeostasis in the inner ear. Therefore, it is important to know the structure and dynamics of KCNE1 to better understand its modulatory role. Previously, the Sanders group solved the three-dimensional structure of KCNE1 in LMPG micelles, which yielded a better understanding of this KCNQ1/KCNE1 channel activity. However, research in the Lorigan group showed different structural properties of KCNE1 when incorporated into POPC/POPG lipid bilayers as opposed to LMPG micelles. It is hence necessary to study the structure of KCNE1 in a more native-like environment such as multi-lamellar vesicles. In this study, the dynamics of lipid bilayers upon incorporation of the membrane protein KCNE1 were investigated using31P solid-state nuclear magnetic resonance (NMR) spectroscopy. Specifically, the protein/lipid interaction was studied at varying molar ratios of protein to lipid content. The static31P NMR and T1relaxation time were investigated. The31P NMR powder spectra indicated significant perturbations of KCNE1 on the phospholipid headgroups of multi-lamellar vesicles as shown from the changes in the31P spectral line shape and the chemical shift anisotropy line width.31P T1relaxation times were shown to be reversely proportional to the molar ratios of KCNE1 incorporated. The31P NMR data clearly indicate that KCNE1 interacts with the membrane. Copyright © 2017 John Wiley & Sons, Ltd.
authors.affiliation: Cell, Molecular, and Structural Biology Graduate Program, Miami University, Oxford, OH, 45056, USA.|Department of Chemistry and Biochemistry, Miami University, Oxford, OH, 45056, USA.
authors.forename: Rongfu
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Chemistry and Biochemistry, Miami University, Oxford, OH, 45056, USA.
authors.forename: Indra D
authors.initials: ID
authors.lastname: Sahu
authors.affiliation: Department of Chemistry and Biochemistry, Miami University, Oxford, OH, 45056, USA.
authors.forename: Raven G
authors.initials: RG
authors.lastname: Comer
authors.affiliation: Department of Chemistry and Biochemistry, Miami University, Oxford, OH, 45056, USA.
authors.forename: Sergey
authors.initials: S
authors.lastname: Maltsev
authors.affiliation: Cell, Molecular, and Structural Biology Graduate Program, Miami University, Oxford, OH, 45056, USA.|Department of Chemistry and Biochemistry, Miami University, Oxford, OH, 45056, USA.
authors.forename: Carole
authors.identifier: http://orcid.org/0000-0003-1347-3870
authors.initials: C
authors.lastname: Dabney-Smith
authors.affiliation: Cell, Molecular, and Structural Biology Graduate Program, Miami University, Oxford, OH, 45056, USA.|Department of Chemistry and Biochemistry, Miami University, Oxford, OH, 45056, USA.
authors.forename: Gary A
authors.identifier: http://orcid.org/0000-0002-2395-3459
authors.initials: GA
authors.lastname: Lorigan
mesh_terms: D000595:Amino Acid Sequence; D006801:Humans; D007700:Kinetics; D008051:Lipid Bilayers / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D024642:Potassium Channels, Voltage-Gated / Q000737:chemistry*
chemical_list: C489622:KCNE1 protein, human; D008051:Lipid Bilayers; D008823:Micelles; D024642:Potassium Channels, Voltage-Gated
keywords: 31P solid-state NMR; KCNE1; lipid bilayer; multi-lamellar vesicles