Forster M J, Mulloy B, Nermut M V
Informatics Laboratory, National Institute for Standards and Control, South Mimms, Herfordshire, UK.
J Mol Biol. 2000 May 19;298(5):841-57. doi: 10.1006/jmbi.2000.3715.
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 rationalizes 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.
基质蛋白p17gag（MA）是gag基因编码的多蛋白（pr55gag）经蛋白水解切割后的产物，在HIV颗粒成熟过程中形成。MA蛋白与病毒膜的内表面相关联，并决定病毒粒子的整体形状。先前的研究表明，MA在溶液和晶体状态下均存在三聚体。在此，我们使用分子建模方法来确定MA三聚体对之间可能的相互作用，并将其与电子显微镜的结构数据相关联。一个系统的搜索对接程序能够识别出一对三聚体的许多能量有利构象，包括一些先前已报道的构象。这些构象被用于生成几个MA三聚体网络，然后根据MA网络的结构观察进行评估。这里提出的模型与实验数据如gag蛋白环之间的间距、糖蛋白（gp41-gp120）瘤的数量和分布以及病毒粒子中MA的拷贝数等有很好的匹配。它还解释了观察到的病毒粒子大小分布，并与成熟HIV中二十面体组织的存在一致。用明确的水和抗衡离子进行能量最小化，以识别参与三聚体间相互作用的残基。这些相互作用的性质与HIV和SIV MA蛋白序列的报道变体中这些残基的保守性相关进行了讨论。
