Laboratory of Physical Chemistry, ETH Zurich, Zurich, Switzerland.
Center for Cellular Imaging and NanoAnalytics, Biozentrum University of Basel, Basel, Switzerland.
Nat Struct Mol Biol. 2017 Feb;24(2):187-193. doi: 10.1038/nsmb.3345. Epub 2016 Dec 26.
High-density lipoprotein (HDL) particles are cholesterol and lipid transport containers. Mature HDL particles destined for the liver develop through the formation of intermediate discoidal HDL particles, which are the primary acceptors for cholesterol. Here we present the three-dimensional structure of reconstituted discoidal HDL (rdHDL) particles, using a shortened construct of human apolipoprotein A-I, determined from a combination of nuclear magnetic resonance (NMR), electron paramagnetic resonance (EPR) and transmission electron microscopy (TEM) data. The rdHDL particles feature a protein double belt surrounding a lipid bilayer patch in an antiparallel fashion. The integrity of this structure is maintained by up to 28 salt bridges and a zipper-like pattern of cation-π interactions between helices 4 and 6. To accommodate a hydrophobic interior, a gross 'right-to-right' rotation of the helices after lipidation is necessary. The structure reflects the complexity required for a shuttling container to hold a fluid lipid or cholesterol interior at a protein:lipid ratio of 1:50.
高密度脂蛋白(HDL)颗粒是胆固醇和脂质的运输容器。成熟的 HDL 颗粒通过形成中间盘状 HDL 颗粒而向肝脏发展,盘状 HDL 颗粒是胆固醇的主要接受体。在这里,我们使用人类载脂蛋白 A-I 的缩短构建体,结合核磁共振(NMR)、电子顺磁共振(EPR)和透射电子显微镜(TEM)数据,确定了重组盘状 HDL(rdHDL)颗粒的三维结构。rdHDL 颗粒的特点是蛋白质双带以反平行方式围绕脂质双层斑块。多达 28 个盐桥和螺旋 4 和 6 之间的拉链式阳离子-π 相互作用模式维持了这种结构的完整性。为了适应疏水环境,在酰化后需要进行螺旋的大致“从右到右”旋转。该结构反映了作为穿梭容器的必需的复杂性,以在蛋白质:脂质比为 1:50 的情况下容纳流体脂质或胆固醇内部。