Molecular dynamics simulations of discoidal bilayers assembled from truncated human lipoproteins
Molecular dynamics simulations of discoidal bilayers assembled from truncated human lipoproteins
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DOI：
10.1529/biophysj.104.046896
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发表时间：
2005-01-01
影响因子：
3.4
通讯作者：
Schulten, K
中科院分区：
文献类型：
--
作者：
Shih, AY;Denisov, IG;Schulten, K
人载脂蛋白 A-1 (apo A-1) 是高密度脂蛋白的主要蛋白质成分。 apo A-1 脂质结合结构域被用作合成称为膜支架蛋白的两亲性螺旋蛋白的模板，用于自组装称为 Nanodiscs 的可溶性单分散盘状颗粒。在这些颗粒中，膜支架蛋白以带状方式围绕脂质双层，形成离散尺寸和组成的双层盘。在这里，我们通过分子动力学模拟研究纳米圆盘的结构，其中纳米圆盘是由不同长度的支架蛋白构建的。模拟显示平面或变形的纳米圆盘取决于支架蛋白的最佳长度和排列。根据每个脂质的平均表面积计算、小角度 X 射线散射曲线的比较以及由截短的支架蛋白制成的 Nanodisc 的相对平面形状，可以得出结论，200 个残基的 apo A-1 脂质结合结构域的前 17 至 18 个残基不参与脂质双层周围的蛋白质“带”的形成。为了确定添加完整膜蛋白是否对 Nanodisc 的整体结构有影响，将细菌视紫红质嵌入纳米圆盘中，并使用分子动力学进行模拟，显示出一个略呈矩形的平面圆盘。
Human apolipoprotein A-1 (apo A-1) is the major protein component of high- density lipoproteins. The apo A-1 lipid-binding domain was used as a template for the synthesis of amphipathic helical proteins termed membrane scaffold proteins, employed to self-assemble soluble monodisperse discoidal particles called Nanodiscs. In these particles, membrane scaffold proteins surround a lipid bilayer in a beltlike fashion forming bilayer disks of discrete size and composition. Here we investigate the structure of Nanodiscs through molecular dynamics simulations in which Nanodiscs were built from scaffold proteins of various lengths. The simulations showed planar or deformed Nanodiscs depending on optimal length and alignment of the scaffold proteins. Based on mean surface area per lipid calculations, comparison of small-angle x-ray scattering curves, and the relatively planar shape of Nanodiscs made from truncated scaffold proteins, one can conclude that the first 17 to 18 residues of the 200-residue apo A-1 lipid-binding domain are not involved in formation of the protein "belts'' surrounding the lipid bilayer. To determine whether the addition of an integral membrane protein has an effect on the overall structure of a Nanodisc, bacteriorhodopsin was embedded into a Nanodisc and simulated using molecular dynamics, revealing a planar disk with a slightly rectangular shape.