The Impact of Viral RNA on the Association Rates of Capsid Protein Assembly: Bacteriophage MS2 as a Case Study
The Impact of Viral RNA on the Association Rates of Capsid Protein Assembly: Bacteriophage MS2 as a Case Study
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DOI：
10.1016/j.jmb.2010.05.037
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发表时间：
2010-07-23
影响因子：
5.6
通讯作者：
Twarock, Reidun
中科院分区：
文献类型：
--
作者：
ElSawy, Karim M.;Caves, Leo S. D.;Twarock, Reidun
大量单链RNA病毒构成了所有病毒的主要类别，共同组装其蛋白质容器和基因组材料。目前人们对病毒基因组在此过程中的多重作用的了解还只是部分。最近的实验结果表明，RNA 除了作为遗传信息库的功能外，还可以在病毒蛋白容器的组装过程中发挥重要的功能作用。因此，研究基因组 RNA 对蛋白质亚基关联的影响可能会为病毒组装机制提供进一步的见解。我们在此研究病毒组装过程中病毒 RNA 对衣壳蛋白关联率的影响。作为案例研究，我们考虑噬菌体 MS2 的病毒衣壳，它由 60 个不对称 (AB) 和 30 个对称 (CC) 蛋白二聚体形成。使用布朗动力学模拟，我们研究了 RNA 茎环（翻译抑制子）的结合对衣壳蛋白二聚体关联率的影响。我们的分析表明，翻译阻遏蛋白结合导致 AB 二聚体的自关联被抑制，而 AB 与 CC 二聚体的关联大大增强。这为实验结果提供了解释，其中观察到 AB 和 CC 二聚体交替组装模式添加到生长的组装中间体中是组装的主要模式。因此，RNA 的存在极大地减少了主要组装途径的数量，从而降低了这些病毒自组装过程的复杂性。 (C) 2010 Elsevier Ltd. 保留所有权利。
A large number of single-stranded RNA viruses, which form a major class of all viruses, co-assemble their protein container and their genomic material. The multiple roles of the viral genome in this process are presently only partly understood. Recent experimental results indicate that RNA, in addition to its function as a repository for genetic information, could play important functional roles during the assembly of the viral protein containers. An investigation of the impact of genomic RNA on the association of the protein subunits may therefore provide further insights into the mechanism of virus assembly. We study here the impact of viral RNA on the association rates of the capsid proteins during virus assembly. As a case study, we consider the viral capsid of bacteriophage MS2, which is formed from 60 asymmetric (AB) and 30 symmetric (CC) protein dimers. Using Brownian dynamics simulations, we investigate the effect of the binding of an RNA stem loop (the translational repressor) on the association rates of the capsid protein dimers. Our analysis shows that translational repressor binding results in self-association of AB dimers being inhibited, whilst association of AB with CC dimers is greatly enhanced. This provides an explanation for experimental results in which an alternating assembly pattern of AB and CC dimer addition to the growing assembly intermediate has been observed to be the dominant mode of assembly. The presence of the RNA hence dramatically decreases the number of dominant assembly pathways and thereby reduces the complexity of the self-assembly process of these viruses. (C) 2010 Elsevier Ltd. All rights reserved.