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首页> 外文期刊>Journal of Molecular Biology >The Role of Packaging Sites in Efficient and Specific Virus Assembly
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The Role of Packaging Sites in Efficient and Specific Virus Assembly

机译：打包站点在高效和特定病毒组装中的作用

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During the life cycle of many single-stranded RNA viruses, including many human pathogens, a protein shell called the capsid spontaneously assembles around the viral genome. Understanding the mechanisms by which capsid proteins selectively assemble around the viral RNA amidst diverse host RNAs is a key question in virology. In one proposed mechanism, short sequences (packaging sites) within the genomic RNA promote rapid and efficient assembly through specific interactions with the capsid proteins. In this work, we develop a coarse-grained particle-based computational model for capsid proteins and RNA that represents protein RNA interactions arising both from nonspecific electrostatics and from specific packaging site interactions. Using Brownian dynamics simulations, we explore how the efficiency and specificity of assembly depend on solution conditions (which control protein protein and nonspecific protein RNA interactions) and the strength and number of packaging sites. We identify distinct regions in parameter space in which packaging sites lead to highly specific assembly via different mechanisms and others in which packaging sites lead to kinetic traps. We relate these computational predictions to in vitro assays for specificity in which cognate viral RNAs compete against non-cognate RNAs for assembly by capsid proteins. (C) 2015 Elsevier Ltd. All rights reserved.
机译：在许多单链RNA病毒（包括许多人类病原体）的生命周期中，被称为衣壳的蛋白质壳自发地在病毒基因组周围组装。了解衣壳蛋白在多种宿主RNA中选择性组装在病毒RNA周围的机制是病毒学中的关键问题。在一种提出的机制中，基因组RNA中的短序列（包装位点）通过与衣壳蛋白的特异性相互作用促进了快速而有效的组装。在这项工作中，我们为衣壳蛋白和RNA开发了基于粗颗粒的计算模型，该模型代表了非特异性静电和特定包装位点相互作用引起的蛋白RNA相互作用。使用布朗动力学模拟，我们探索组装的效率和特异性如何取决于溶液条件（控制蛋白质和非特异性蛋白质RNA相互作用）以及包装位点的强度和数量。我们确定参数空间中的不同区域，在这些区域中包装位点通过不同的机制导致高度特定的组装，而在其他区域中包装位点导致动力学陷阱。我们将这些计算预测与体外测定的特异性相关，其中同源病毒RNA与衣壳蛋白组装的非同源RNA竞争。 （C）2015 Elsevier Ltd.保留所有权利。

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