Structural features of cholesteryl ester transfer protein: a molecular dynamics simulation study.
Structural features of cholesteryl ester transfer protein: a molecular dynamics simulation study.
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胆固醇酯转移蛋白的结构特征：分子动力学模拟研究
DOI：
10.1002/prot.24200
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发表时间：
2013-03
影响因子：
2.9
通讯作者：
Zhang, Shengli
中科院分区：
文献类型：
--
作者：
Lei, Dongsheng;Zhang, Xing;Jiang, Shengbo;Cai, Zhaodi;Rames, Matthew J.;Zhang, Lei;Ren, Gang;Zhang, Shengli
胆固醇酯转移蛋白（CETP）介导胆固醇酯从保护动脉粥样硬化的高密度脂蛋白向致动脉粥样硬化的低密度脂蛋白或极低密度脂蛋白的净转移。抑制CETP提高高密度脂蛋白胆固醇（好胆固醇）水平，降低低密度脂蛋白胆固醇（坏胆固醇）水平，使其成为预防和治疗冠心病的有希望的药物靶点。虽然已经确定了CETP的晶体结构，但介导胆固醇酯转移的分子机制尚不清楚，甚至生理环境下CETP的结构特征也尚不清楚。我们进行了分子动力学模拟，以探索CETP在水溶液中的结构特征。结果表明：溶液中n端β-桶状畴远端柔韧性明显大于晶体中；相反，螺旋X的柔韧性稍差。在模拟过程中，c端β-桶状畴的远端扩展，亲水性表面的增加大于疏水性表面的增加。此外，该区域还形成了一个新的表面孔隙。该表面孔和所有空腔在CETP中是稳定的。这些结果表明，在溶液中允许通过连接空腔在CETP内形成连续的隧道。
Cholesteryl ester transfer protein (CETP) mediates the net transfer of cholesteryl esters from atheroprotective high-density lipoproteins to atherogenic low-density lipoproteins or very-low-density lipoproteins. Inhibition of CETP raises high-density lipoprotein cholesterol (good cholesterol) levels and reduces low-density lipoprotein cholesterol (bad cholesterol) levels, making it a promising drug target for the prevention and treatment of coronary heart disease. Although the crystal structure of CETP has been determined, the molecular mechanism mediating cholesteryl esters transfer is still unknown, even the structural features of CETP in a physiological environment remain elusive. We performed molecular dynamics simulations to explore the structural features of CETP in an aqueous solution. Results show that the distal portion flexibility of N-terminal β-barrel domain is considerably greater in solution than in crystal; conversely, the flexibility of helix X is slightly less. During the simulations the distal end of C-terminal β-barrel domain expanded while the hydrophilic surface increasing more than the hydrophobic surface. In addition a new surface pore was generated in this domain. This surface pore and all cavities in CETP are stable. These results suggest that the formation of a continuous tunnel within CETP by connecting cavities is permitted in solution.
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影响因子：
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作者：
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