Molecular modelling study of HIV p17gag (MA) protein shell utilising data from electron microscopy and X-ray crystallography
Molecular modelling study of HIV p17gag (MA) protein shell utilising data from electron microscopy and X-ray crystallography
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DOI：
10.1006/jmbi.2000.3715
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发表时间：
2000-05-19
影响因子：
5.6
通讯作者：
Nermut, MV
中科院分区：
文献类型：
--
作者：
Forster, MJ;Mulloy, B;Nermut, MV
基质蛋白p17 gag（MA）是gag基因编码的多蛋白（pr 55 gag）的蛋白水解裂解产物，并且在HIV颗粒经历成熟过程时形成。MA蛋白与病毒膜的内表面结合，并决定病毒体的整体形状。以前的研究表明，存在的三聚体的MA在溶液中，并在结晶状态。在这里，我们使用分子建模方法来确定可行的MA三聚体对之间的相互作用，并与电子显微镜的结构数据。一个系统的搜索对接程序是能够确定许多积极有利的构象对三聚体，包括一些以前已经报道。这些构象被用来生成几个网络的MA三聚体，然后进行评估对MA网络的结构观察。本文提出的模型与实验数据如gag蛋白环之间的间距、糖蛋白（gp 41-gp 120）球的数目和分布以及病毒颗粒中MA的拷贝数等具有很好的匹配性。这也合理化了观察到的病毒颗粒大小分布，并与成熟HIV中二十面体组织的存在相一致。使用明确的水和反离子进行能量最小化，用于鉴定参与三聚体间相互作用的残基。这些相互作用的性质进行了讨论，这些残基的保护报告的HIV和SIV MA蛋白序列的变体。(C)北京大学出版社.
The matrix protein p17gag (MA) is a product of proteolytic cleavage of the gag gene encoded polyprotein (pr55gag) and is formed when HIV particles undergo the process of maturation. The MA protein is associated with the inner surface of the viral membrane and determines the overall shape of the virion. Previous studies have shown the existence of trimers of MA in solution and in the crystalline state. Here, we used molecular modelling methods to identify feasible interactions between pairs of MA trimers and have related this to structural data from electron microscopy. A systematic search docking procedure was able to identify many energetically favourable conformations for a pair of trimers, including some which have been previously reported. These conformations were used to generate several networks of MA trimers, which were then evaluated against structural observations of the MA network. The model suggested here provides a good match with experimental data such as the spacing between gag protein rings, the number and disposition of glycoprotein (gp41-gp120) knobs and the number of copies of MA in a virus particle. It also rationalises the observed distribution of sizes of virus particles and is consistent with the presence of icosahedral organisation in mature HIV. Energy minimisation performed with explicit water and counter ions, was used to identify residues participating in inter-trimer interactions. The nature of these interactions is discussed in relation to the conservation of these residues in reported variants of the HIV and SIV MA protein sequences. (C) 2000 Academic Press.