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化学进展  2014 

胆固醇酯转移蛋白在胆固醇酯转移中的结构与功能

DOI: 10.7536/PC131028, PP. 879-888

Keywords: 胆固醇酯,胆固醇酯转移蛋白,脂蛋白,透射电子显微镜,分子动力学模拟,结构柔性,通道模型

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Abstract:

人体胆固醇酯转移蛋白(CETP)会造成胆固醇酯从高密度脂蛋白(HDL)向低密度脂蛋白(LDL)或极低密度脂蛋白(VLDL)的转移,从而增加人体患心血管疾病的危险性。了解CETP在胆固醇酯转移过程中的作用和机理,是研发新的CETP抑制剂药物以预防和治疗心血管疾病的重要基础和关键步骤。本文综述了CETP结构与功能领域研究的最新进展,详细介绍了CETP与各类脂蛋白绑定结构的高分辨透射电子显微镜研究;并结合对CETP晶体结构的分析,以及生理溶液中CETP结构与动态特征、CETP与脂滴间相互作用的分子动力学模拟研究结果,阐述并讨论了CETP脂转移机理的“通道”模型;最后对尚待解决的关键问题与未来的研究方向进行了展望,以期促进CETP功能机理的研究和抑制药物的研制。

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