Zimmerman Noah J, Labra Oscar Rojas, Reddy Vijay S
The Hormel Institute, University of Minnesota, Austin, Minnesota, USA.
Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota, USA.
Protein Sci. 2025 Sep;34(9):e70257. doi: 10.1002/pro.70257.
Nonenveloped viruses package, carry, and deliver their genomes to the targeted cells using protein shells known as capsids. The viral capsids come in different shapes and sizes, most exhibiting helical or icosahedral symmetries. Here, we analyzed 634 icosahedral capsids at high resolution (<4 Å) from 39 virus families with T-numbers ranging from 1 to 9 and evaluated the aggregated buried surface areas (BSAs) at the unique interfaces as a measure of capsid strength and protein-protein interactions (PPIs). The BSAs were further analyzed relative to their capsid diameters and the calculated molecular weight (MW) of coat protein subunits (CPs) occupying the icosahedral asymmetric unit (IAU). Our results show that naturally occurring viral capsids exhibit stronger PPIs relative to non-native and/or engineered capsids. Interestingly, the "T = 2" capsids cluster distinctly, exhibiting weaker PPIs relative to their capsid size and subunit MWs. Furthermore, the normalized BSAs by the MW of the CPs present in the IAU are fairly constant across different capsids, suggesting that the extent of the PPIs is proportional to the CP size with a few exceptions (e.g., "T = 2" capsids). We also identified the range of capsid diameters and MWs of CPs forming different T = number capsids, which suggest a CP of 30-50 kDa can be used to build any quasi-equivalent capsid with T-numbers 1-9. Furthermore, we identified the strongest capsids available at various diameters at 25 Å intervals. Taken together, in addition to the targeting specificities, the results from this study are useful for choosing viral capsids for biomedical applications.
无包膜病毒利用被称为衣壳的蛋白质外壳来包装、携带并将其基因组递送至靶细胞。病毒衣壳有不同的形状和大小，大多数呈现螺旋或二十面体对称性。在此，我们以高分辨率（<4Å）分析了来自39个病毒科的634个二十面体衣壳，其T值范围为1至9，并评估了独特界面处的聚集埋藏表面积（BSA），以此作为衣壳强度和蛋白质-蛋白质相互作用（PPI）的一种度量。还相对于衣壳直径以及占据二十面体不对称单元（IAU）的衣壳蛋白亚基（CP）的计算分子量（MW）对BSA进行了进一步分析。我们的结果表明，天然存在的病毒衣壳相对于非天然和/或工程化衣壳表现出更强的PPI。有趣的是，“T = 2”衣壳明显聚类，相对于其衣壳大小和亚基MW而言，表现出较弱的PPI。此外，IAU中存在的CP的MW归一化后的BSA在不同衣壳中相当恒定，这表明PPI的程度与CP大小成正比，少数情况除外（例如，“T = 2”衣壳）。我们还确定了形成不同T值衣壳的衣壳直径和CP的MW范围，这表明30 - 50 kDa的CP可用于构建任何T值为1 - 9的准等效衣壳。此外，我们确定了以25Å间隔在各种直径下最强的衣壳。综上所述，除了靶向特异性外，本研究结果对于选择用于生物医学应用的病毒衣壳很有用。
