报告人：张胜利（西安交通大学）

报告时间：2020年5月26日下午14:00-15:00

腾讯会议ID：564349827

报告摘要：

Cardiovascular disease is the most common and fatal disease in human. Cholesteryl ester transfer protein (CETP) activity can reduce HDL-cholesterol concentrations and CETP deficiency is associated with elevated HDL-cholesterol levels. Despite the intense clinical interest in CETP inhibition, little is known concerning the molecular mechanisms of CETP-mediated lipid transfer among lipoproteins or even how CETP interacts with lipoproteins. In this talk, we present the studies on the lipoproteins to pursuit the cholesteryl ester transfer in human. We perform the molecular dynamics simulations predicting a continuous central tunnel within CETP. We propose a model that cholesteryl ester migrates from HDL to LDL or VLDL through a hydrophobic tunnel structure, the tunnel mechanism. It is directly supported by the experiment observation that CETP bridges HDL to LDL or VLDL to form a ternary complex. Furthermore, we demonstrate the interaction between the CETP and its inhibitors. Those are significant not only to understanding the cholesteryl ester transfer in human but also searching the drugs to the cardiovascular disease.

报告人简介

 张胜利教授长期从事蛋白质结构与功能的物理机制研究工作，课题组具有一台冷冻电镜和大型计算机集群用于实验研究和理论与计算机数值模拟研究。主持完成多项国家自然科学基金项目，先后与美国、新加坡及国内专家学者合作，研究成果在Nat Chem Biol、J Am Chem Soc、J Biol Chem等国际著名学术刊物发表180余篇论文，获教育部自然科学二等奖1项、省科技进步一等奖1项。

本课题组建立了一个新的高密度脂蛋白模型，纠正了之前各成分间不匹配的错误；发现了胆固醇酯转运蛋白的疏水通道，提出了人体中胆固醇酯转运的单体通道模型，并被实验验证。发现了非小细胞肺癌靶点药物抗药性的一个新型机制以及相应的信号通路；虚拟筛选出一个抗生素具有治疗肺动脉高压的新效能，并在动物实验中验证；发现一种老药能够对非小细胞肺癌具有化学预防作用，动物实验证明了其作用有效；研究了一系列蛋白质及miRNA等在癌细胞分裂、扩散、及凋亡中的作用和功能。