Allosteric Control of Icosahedral Capsid Assembly.
Allosteric Control of Icosahedral Capsid Assembly.
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DOI：
10.1021/acs.jpcb.6b02768
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发表时间：
2016-07-07
期刊：
影响因子：
--
通讯作者：
Hagan MF
中科院分区：
文献类型：
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作者：
Lazaro GR;Hagan MF
在病毒的生命周期中，病毒蛋白和其他成分自我组装，形成一个有序的蛋白质外壳，称为衣壳。这一组装过程受到多个相互竞争的限制，包括需要形成一个耐热的外壳，同时避免动力学陷阱。已有研究提出，病毒的组装通过变构调节来满足这些限制，包括不同组装倾向的构象之间衣壳蛋白的相互转换。在这篇文章中，我们使用计算和理论模型来探索这种变构如何影响二十面体壳层的组装。我们模拟了在广泛的蛋白质浓度、蛋白质结合亲和力和两种不同的变构控制机制下的组装。我们发现，在变构控制的阈值强度以上，组装在广泛的亚基结合亲和力和浓度范围内变得健壮，允许形成高度耐热的衣壳。我们的结果表明，变构可以显著改变导致成功组装的蛋白质结合亲和力的范围，因此应该在用于从实验数据估计相互作用参数的模型中得到解释。
During the lifecycle of a virus, viral proteins and other components self-assemble to form an ordered protein shell called a capsid. This assembly process is subject to multiple competing constraints, including the need to form a thermostable shell while avoiding kinetic traps. It has been proposed that viral assembly satisfies these constraints through allosteric regulation, including the interconversion of capsid proteins among conformations with different propensities for assembly. In this article we use computational and theoretical modeling to explore how such allostery affects the assembly of icosahedral shells. We simulate assembly under a wide range of protein concentrations, protein binding affinities, and two different mechanisms of allosteric control. We find that, above a threshold strength of allosteric control, assembly becomes robust over a broad range of subunit binding affinities and concentrations, allowing the formation of highly thermostable capsids. Our results suggest that allostery can significantly shift the range of protein binding affinities that lead to successful assembly, and thus should be accounted for in models that are used to estimate interaction parameters from experimental data.