A型流感病毒基质蛋白M1的二聚化机制  

Dimerization Mechanisms of Influenza A Virus Matrix Protein M1

作　　者：张一堪 曹密 刘建平[1] 黄强[1,3] 

机构地区：[1]复旦大学生命科学学院遗传工程国家重点实验室,上海200438 [2]国家蛋白质科学中心(上海),上海201203 [3]上海生物制造技术协同创新中心,上海200237

出　　处：《复旦学报（自然科学版）》2016年第3期388-395,共8页Journal of Fudan University：Natural Science

基　　金：国家自然科学基金(91430112);上海市自然科学基金(13ZR1402400)

摘　　要：流感病毒基质蛋白1(matrix protein 1,M1)位于病毒包膜之下,形成一层壳状结构(衣壳),可与病毒的血凝素、神经氨酸酶、包膜和病毒遗传物质发生相互作用,在病毒的组装与复制过程中起着关键作用.不过,除N端有晶体结构外,全长M1蛋白的结构尚未解析.因此,人们对全长M1蛋白如何二聚化、然后多聚化形成病毒衣壳的过程知之甚少.为了解M1蛋白的二聚化机制,首先从M1的N端片段晶体结构出发,用蛋白质结构预测方法获得M1的全长结构模型;其次,对可能的M1二聚体进行分子动力学模拟,分析其二聚化界面的氨基酸,由此发现了一种通过M1蛋白C端片段结合而形成的二聚体;最后,为验证模拟结果,用电镜三维重构方法分析了全长M1二聚体的构象,并提出了M1多聚化的机理模型.Influenza A virus matrix protein 1 （M1） forms the viral capsid under the viral membrane, and interacts with hemagglutinin（HA）,neuraminidase（NA）,membrane and RNA simultaneously. However, crystal structures are only available for the N-terminal segment of M1. Little is known about the dimerization of the full-length M1 proteins that is required for the polymerization to form the capsid. To understand the dimerization mechanism of M1, here we used homology modeling to predict the structure of the full-length M1 on the basis of the N-terminal structure. Then, we carried out molecular dynamics（MD） simulation for the possible M1 dimers, and analyzed the amino acids of the dimerization interfaces. The results of MD simulation indicated there is a new dimerization interface formed by the interactions of two M1 C-terminal segments. To verify the results, we analyzed the M1 dimers by the single-particle 3D reconstruction of electron microscopy, and thereby presented a mechanistic model for the M1 polymerization.

关 键 词：A型流感病毒 基质蛋白M1 二聚化 分子建模 单颗粒三维重构 

分 类 号：Q71[生物学—分子生物学]