Predicting the structure of apolipoprotein A-1 in reconstituted high-density lipoprotein disks
Predicting the structure of apolipoprotein A-1 in reconstituted high-density lipoprotein disks
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DOI：
10.1016/s0006-3495(97)78264-x
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发表时间：
1997-11-01
影响因子：
3.4
通讯作者：
Schulten, K
中科院分区：
文献类型：
--
作者：
Phillips, JC;Wriggers, W;Schulten, K
在重组的高密度脂蛋白中，载脂蛋白a- 1和磷脂酰胆碱结合形成圆盘，其中载脂蛋白a- 1的两亲性α -螺旋结合到脂质双分子层核心的边缘，保护水性脂质尾部不受水环境的影响。我们利用实验数据、序列分析和分子建模，构建了由两种载脂蛋白a - i蛋白和160种棕榈酰磷脂酰胆碱脂组成的高密度脂蛋白盘的原子模型。载脂蛋白A-I的初始球形结构域（1-47）被排除在模型之外，与8埃的水分子壳层水合。采用分子动力学和模拟退火方法对模型的稳定性进行了检验。在我们的模拟中，蛋白质包含并粘附在脂质双分子层上，同时提供了良好的脂质尾部覆盖。
In reconstituted high-density lipoproteins, apolipoprotein A-I and phosphatidylcholines combine to form disks in which the amphipathic alpha-helices of apolipoprotein A-1 bind to the edge of a lipid bilayer core, shielding the hydrophic lipid tails from the aqueous environment. We have employed experimental data, sequence analysis, and molecular modeling to construct an atomic model of such a reconstituted high-density lipoprotein disk consisting of two apolipoprotein A-I proteins and 160 palmitoyloleoylphosphatidylcholine lipids. The initial globular domain (1-47) of apolipoprotein A-I was excluded from the model, which was hydrated with an 8-Angstrom shell of water molecules. Molecular dynamics and simulated annealing were used to test the stability of the model. Both head-to-tail and head-to-head forms of a reconstituted high-density lipoprotein were simulated, In our simulations the protein contained and adhered to the lipid bilayer while providing good coverage of the lipid tails.