A Multiscale Model for the Self-Assembly of Coat Proteins in Bacteriophage MS2
A Multiscale Model for the Self-Assembly of Coat Proteins in Bacteriophage MS2
复制标题
噬菌体 MS2 中外壳蛋白自组装的多尺度模型
DOI：
10.1021/acs.jcim.9b00514
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发表时间：
2019
影响因子：
5.6
通讯作者：
Wu, Yinghao
中科院分区：
文献类型：
--
作者：
Wang, Bo;Zhang, Junjie;Wu, Yinghao
病毒衣壳的自组装是感染性病毒形成的重要步骤。阐明衣壳或病毒样颗粒如何组装的动力学机制可以推进我们对病毒生命周期的了解，以及生物材料自组装的一般原理。然而，目前对许多病毒的衣壳组装的理解仍然是不完整的，这是由于沿着组装途径的瞬时中间体沿着在实验上难以检测的事实。在本文中，我们构建了一个新的多尺度计算框架来模拟病毒样粒子的自组装。我们将我们的方法应用于噬菌体MS2的外壳蛋白作为一个特定的模型系统。这种噬菌体MS2的病毒样颗粒具有独特的特征，其90个序列相同的二聚体可以分为两个结构不同的组：一个是对称的CC二聚体，另一个是不对称的AB二聚体。AB二聚体之间的同型相互作用导致5倍对称接触，而AB和CC二聚体之间的异型相互作用导致6倍对称接触。我们发现，组装可以被描述为一个物理过程的相变，这是由各种因素，如浓度和特定的化学计量之间的AB和CC二聚体。我们的模拟还表明，异型和同型接口发挥独特的作用，在调节组装动力学。AB和CC二聚体之间的相互作用比两个AB二聚体之间的相互作用更具动态性。因此，我们认为，通过异型二聚体相互作用的病毒衣壳的交替生长占主导地位的组装途径。据我们所知，这是第一个模拟噬菌体MS2外壳蛋白组装过程的多尺度模型。这种方法的普遍性为其在其他病毒衣壳、病毒样颗粒和新型药物递送系统的组装中的进一步应用打开了大门。
The self-assembly of viral capsids is an essential step to the formation of infectious viruses. Elucidating the kinetic mechanisms of how a capsid or virus-like particle assembles could advance our knowledge about the viral lifecycle, as well as the general principles in self-assembly of biomaterials. However, current understanding of capsid assembly remains incomplete for many viruses due to the fact that the transient intermediates along the assembling pathways are experimentally difficult to be detected. In this paper, we constructed a new multiscale computational framework to simulate the self-assembly of virus-like particles. We applied our method to the coat proteins of bacteriophage MS2 as a specific model system. This virus-like particle of bacteriophage MS2 has a unique feature that its 90 sequence-identical dimers can be classified into two structurally various groups: one is the symmetric CC dimer, and the other is the asymmetric AB dimer. The homotypic interactions between AB dimers result in a 5-fold symmetric contact, while the heterotypic interactions between AB and CC dimers result in 6-fold symmetric contact. We found that the assembly can be described as a physical process of phase transition that is regulated by various factors such as concentration and specific stoichiometry between AB and CC dimers. Our simulations also demonstrate that heterotypic and homotypic interfaces play distinctive roles in modulating the assembling kinetics. The interaction between AB and CC dimers is much more dynamic than that between two AB dimers. We therefore suggest that the alternate growth of viral capsid through the heterotypic dimer interactions dominates the assembling pathways. This is, to the best of our knowledge, the first multiscale model to simulate the assembling process of coat proteins in bacteriophage MS2. The generality of this approach opens the door to its further applications in assembly of other viral capsids, virus-like particles, and novel drug delivery systems.
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DOI：
10.1073/pnas.1707102114
发表时间：
2017-10-01
影响因子：
11.1
作者：
Cui, Zhicheng;Gorzelnik, Karl V.;Zhang, Junjie
通讯作者：
Zhang, Junjie
亚基 FG 环发生突变的 MS2 衣壳的晶体结构。
影响因子：
5.6
作者：
N. Stonehouse;K. Valegård;K. Valegård;R. Golmohammadi;R. Golmohammadi;S. Worm;S. Worm;Catherine Walton;Catherine Walton;Peter G. Stockley;Peter G. Stockley;L. Liljas;L. Liljas
通讯作者：
L. Liljas
影响因子：
3.3
作者：
Shirvanyants, David;Ding, Feng;Tsao, Douglas;Ramachandran, Srinivas;Dokholyan, Nikolay V.
通讯作者：
Dokholyan, Nikolay V.
生物分子软物质的自组装。
影响因子：
3.4
作者：
Stupp SI;Zha RH;Palmer LC;Cui H;Bitton R
通讯作者：
Bitton R
DOI：
10.1016/j.str.2018.07.010
发表时间：
2018-10-02
期刊：
Structure (London, England : 1993)
影响因子：
--
作者：
Wang B;Xie ZR;Chen J;Wu Y
通讯作者：
Wu Y