Coarse-grained simulation reveals key features of HIV-1 capsid self-assembly.
Coarse-grained simulation reveals key features of HIV-1 capsid self-assembly.
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DOI：
10.1038/ncomms11568
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发表时间：
2016-05-13
影响因子：
16.6
通讯作者：
Voth GA
中科院分区：
文献类型：
--
作者：
Grime JMA;Dama JF;Ganser-Pornillos BK;Woodward CL;Jensen GJ;Yeager M;Voth GA
HIV - 1病毒颗粒的成熟对病毒的感染性至关重要。在成熟过程中，许多份衣壳蛋白（CA）自组装成衣壳，包裹病毒RNA。衣壳组装起始和早期阶段的机制细节仍有待阐明。我们在各种条件下对衣壳组装进行了粗粒度模拟，不仅考虑了衣壳晶格的自组装，还考虑了衣壳在进入靶细胞细胞质时可能发生的拆解。描述了CA浓度、分子拥挤程度以及CA构象可变性的影响，结果表明衣壳成核和生长是一个多阶段过程，需要明确的亚稳态中间体。成熟衣壳晶格的形成对局部条件敏感，CA浓度和分子拥挤程度相对细微的变化会影响自组装以及结构形态的整体情况。
在未成熟的HIV病毒粒子转化为成熟的感染形式过程中会发生显著的形态变化。在此，作者使用粗粒度分子动力学模拟来模拟HIV - 1衣壳的自组装和拆解事件，结果表明存在几种对局部条件敏感的亚稳态衣壳中间体。
The maturation of HIV-1 viral particles is essential for viral infectivity. During maturation, many copies of the capsid protein (CA) self-assemble into a capsid shell to enclose the viral RNA. The mechanistic details of the initiation and early stages of capsid assembly remain to be delineated. We present coarse-grained simulations of capsid assembly under various conditions, considering not only capsid lattice self-assembly but also the potential disassembly of capsid upon delivery to the cytoplasm of a target cell. The effects of CA concentration, molecular crowding, and the conformational variability of CA are described, with results indicating that capsid nucleation and growth is a multi-stage process requiring well-defined metastable intermediates. Generation of the mature capsid lattice is sensitive to local conditions, with relatively subtle changes in CA concentration and molecular crowding influencing self-assembly and the ensemble of structural morphologies. Significant morphological changes occur during the conversion of the immature HIV virion into a mature infectious form. Here the authors use coarse-grained molecular dynamics simulations to model HIV-1 capsid self-assembly and disassembly events that suggests several metastable capsid intermediates sensitive to local conditions.