Simulated Self-Assembly of the HIV-1 Capsid: Protein Shape and Native Contacts Are Sufficient for Two-Dimensional Lattice Formation
Simulated Self-Assembly of the HIV-1 Capsid: Protein Shape and Native Contacts Are Sufficient for Two-Dimensional Lattice Formation
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DOI：
10.1016/j.bpj.2011.05.025
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发表时间：
2011-06-22
影响因子：
3.4
通讯作者：
Tycko, Robert
中科院分区：
文献类型：
--
作者：
Chen, Bo;Tycko, Robert
我们报告的Monte Carlo模拟的HIV-1衣壳蛋白（CA）的自组装的初始阶段，使用粗粒度的表示，模仿CA的骨干结构和实验观察到的分子间接触。N-末端结构域/N-末端结构域和N-末端结构域/C-末端结构域相互作用的简单表示，加上正确的蛋白质形状，足以驱动在二维中具有正确六边形对称性的有序晶格的形成。我们推导出一个近似的浓度/温度相图晶格形成，我们调查的途径，晶格发展从最初分离的CA二聚体。在该模型中，晶格形成发生在两个阶段：1）CA二聚体缩合成无序簇;和2）通过簇内一个六聚体单元的出现使晶格成核。CA二聚体的三聚体是重要的早期中间体，并且五聚体在簇内是亚稳定的。在蒙特卡罗运行开始时引入预形成的六聚体并不直接形成晶格，但确实促进了大簇的形成。我们讨论了这些模拟和实验观察CA组装在HIV-1和体外之间可能存在的联系。
We report Monte Carlo simulations of the initial stages of self-assembly of the HIV-1 capsid protein (CA), using a coarse-grained representation that mimics the CA backbone structure and intermolecular contacts observed experimentally. A simple representation of N-terminal domain/N-terminal domain and N-terminal domain/C-terminal domain interactions, coupled with the correct protein shape, is sufficient to drive formation of an ordered lattice with the correct hexagonal symmetry in two dimensions. We derive an approximate concentration/temperature phase diagram for lattice formation, and we investigate the pathway by which the lattice develops from initially separated CA dimers. Within this model, lattice formation occurs in two stages: 1), condensation of CA dimers into disordered clusters; and 2), nucleation of the lattice by the appearance of one hexamer unit within a cluster. Trimers of CA dimers are important early intermediates, and pentamers are metastable within clusters. Introduction of a preformed hexamer at the beginning of a Monte Carlo run does not directly seed lattice formation, but does facilitate the formation of large clusters. We discuss possible connections between these simulations and experimental observations concerning CA assembly within HIV-1 and in vitro.