Should Virus Capsids Assemble Perfectly? Theory and Observation of Defects
Should Virus Capsids Assemble Perfectly? Theory and Observation of Defects
复制标题
病毒衣壳应该完美组装吗？
DOI：
10.1016/j.bpj.2020.09.021
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发表时间：
2020
影响因子：
3.4
通讯作者：
Zuckerman, Daniel M.
中科院分区：
文献类型：
--
作者：
Spiriti, Justin;Conway, James F.;Zuckerman, Daniel M.
虽然已发表的病毒衣壳结构模型通常表现出高度的规则性或对称性，但由于衣壳组装的波动环境以及基因组递送前某些衣壳需要拆卸，因此可能会出现结构缺陷。在计算机模拟中观察到缺陷结构，并且在单粒子冷冻电子显微镜研究中是明显的。在这里，我们量化的条件下，可能会出现缺陷，使用统计力学模型，允许理想的，有缺陷的，和空置的网站。该模型显示了亲和力参数的阈值，低于该阈值存在明显的缺陷衣壳群体。即使不允许有缺陷的网站，通常也会有一些空缺。冷冻电子显微镜显微照片中单个颗粒的分析产生了15%的缺陷颗粒的确认。我们的研究结果表明，病毒衣壳的结构异质性可能被低估，也指出了一个非传统的组装抑制策略。
Although published structural models of viral capsids generally exhibit a high degree of regularity or symmetry, structural defects might be expected because of the fluctuating environment in which capsids assemble and the requirement of some capsids for disassembly before genome delivery. Defective structures are observed in computer simulations, and are evident in single-particle cryoelectron microscopy studies. Here, we quantify the conditions under which defects might be expected, using a statistical mechanics model allowing for ideal, defective, and vacant sites. The model displays a threshold in affinity parameters below which there is an appreciable population of defective capsids. Even when defective sites are not allowed, there is generally some population of vacancies. Analysis of single particles in cryoelectron microscopy micrographs yields a confirmatory ≳15% of defective particles. Our findings suggest structural heterogeneity in virus capsids may be under-appreciated, and also points to a nontraditional strategy for assembly inhibition.