Solution structure of discoidal high-density lipoprotein particles with a shortened apolipoprotein A-I
Solution structure of discoidal high-density lipoprotein particles with a shortened apolipoprotein A-I
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DOI：
10.1038/nsmb.3345
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发表时间：
2017-02-01
影响因子：
16.8
通讯作者：
Riek, Roland
中科院分区：
文献类型：
--
作者：
Bibow, Stefan;Polyhach, Yevhen;Riek, Roland
高密度脂蛋白（HDL）颗粒是胆固醇和脂质运输的容器。成熟的高密度脂蛋白颗粒通过形成中间盘状高密度脂蛋白颗粒进入肝脏，盘状高密度脂蛋白颗粒是胆固醇的主要受体。通过核磁共振（NMR）、电子顺磁共振（EPR）和透射电子显微镜（TEM）数据，我们展示了重组盘状高密度脂蛋白（rdHDL）颗粒的三维结构，利用人类载脂蛋白a - i的缩短结构。rdHDL颗粒以反平行方式围绕脂质双分子层斑块的蛋白质双带为特征。这种结构的完整性由多达28个盐桥和螺旋4和6之间的阳离子- π相互作用的拉链状模式维持。为了容纳疏水的内部，脂化后螺旋的“从右到右”旋转是必要的。这种结构反映了一个穿梭容器以1:50的蛋白脂比容纳液体脂质或胆固醇所需的复杂性。
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-pi 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.