Spiriti Justin, Conway James F, Zuckerman Daniel M
Department of Biomedical Engineering, Oregon Health and Science University, Portland, Oregon.
Department of Structural Biology, University of Pittsburgh, Pittsburgh, Pennsylvania.
Biophys J. 2020 Nov 3;119(9):1781-1790. doi: 10.1016/j.bpj.2020.09.021. Epub 2020 Sep 28.
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.
尽管已发表的病毒衣壳结构模型通常呈现出高度的规则性或对称性，但由于衣壳组装所处的环境波动以及某些衣壳在基因组传递前需要解体，因此可能会出现结构缺陷。在计算机模拟中观察到了有缺陷的结构，并且在单颗粒冷冻电子显微镜研究中也很明显。在这里，我们使用一个允许存在理想、有缺陷和空位的统计力学模型，对可能出现缺陷的条件进行了量化。该模型在亲和参数上显示出一个阈值，低于该阈值时会有相当数量的有缺陷衣壳。即使不允许存在有缺陷的位点，通常也会有一些空位。对冷冻电子显微镜显微照片中的单颗粒进行分析，得出约15%的有缺陷颗粒的确认结果。我们的研究结果表明，病毒衣壳中的结构异质性可能未得到充分认识，同时也指出了一种非传统的组装抑制策略。
