Zhang Rongfu, Sahu Indra D, Comer Raven G, Maltsev Sergey, Dabney-Smith Carole, Lorigan Gary A
Cell, Molecular, and Structural Biology Graduate Program, Miami University, Oxford, OH, 45056, USA.
Department of Chemistry and Biochemistry, Miami University, Oxford, OH, 45056, USA.
Magn Reson Chem. 2017 Aug;55(8):754-758. doi: 10.1002/mrc.4589. Epub 2017 Mar 16.
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 using P solid-state nuclear magnetic resonance (NMR) spectroscopy. Specifically, the protein/lipid interaction was studied at varying molar ratios of protein to lipid content. The static P NMR and T relaxation time were investigated. The P NMR powder spectra indicated significant perturbations of KCNE1 on the phospholipid headgroups of multi-lamellar vesicles as shown from the changes in the P spectral line shape and the chemical shift anisotropy line width. P T relaxation times were shown to be reversely proportional to the molar ratios of KCNE1 incorporated. The P NMR data clearly indicate that KCNE1 interacts with the membrane. Copyright © 2017 John Wiley & Sons, Ltd.
已知KCNE1可调节电压门控钾通道α亚基KCNQ1，以产生缓慢激活的钾电流。这种钾通道对于介导心跳的心脏动作电位以及内耳中的钾离子稳态至关重要。因此，了解KCNE1的结构和动力学对于更好地理解其调节作用很重要。此前，桑德斯团队解析了KCNE1在LMPG胶束中的三维结构，这有助于更好地理解该KCNQ1/KCNE1通道的活性。然而，洛里根团队的研究表明，与LMPG胶束相比，KCNE1整合到POPC/POPG脂质双层中时具有不同的结构特性。因此，有必要在更接近天然的环境（如多层囊泡）中研究KCNE1的结构。在本研究中，使用磷固态核磁共振（NMR）光谱研究了膜蛋白KCNE1整合后脂质双层的动力学。具体而言，研究了蛋白质与脂质含量不同摩尔比下的蛋白质/脂质相互作用。研究了静态磷NMR和T弛豫时间。磷NMR粉末光谱表明，从磷谱线形状和化学位移各向异性线宽的变化可以看出，KCNE1对多层囊泡的磷脂头部基团有显著扰动。磷T弛豫时间与整合的KCNE1摩尔比成反比。磷NMR数据清楚地表明KCNE1与膜相互作用。版权所有©2017约翰威立父子有限公司。
