Principles for enhancing virus capsid capacity and stability from a thermophilic virus capsid structure
Principles for enhancing virus capsid capacity and stability from a thermophilic virus capsid structure
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DOI：
10.1038/s41467-019-12341-z
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发表时间：
2019-10-02
影响因子：
16.6
通讯作者：
Kelch，Brian A.
中科院分区：
文献类型：
--
作者：
Stone，Nicholas P.;Demo，Gabriel;Kelch，Brian A.
双链DNA病毒的衣壳保护病毒基因组免受恶劣的细胞外环境的影响，同时保持稳定性以抵抗包装DNA的高内部压力。为了阐明衣壳如何在极端环境中保持稳定性，我们使用冷冻电子显微镜来确定热稳定噬菌体P74-26的衣壳结构到2.8-kDa分辨率。我们发现P74-26衣壳表现出与其他尾噬菌体非常相似的整体结构，使我们能够直接比较结构以获得增强稳定性的结构基础。我们的结构揭示了套索样的相互作用，似乎像捕捉债券的功能。这种结构允许衣壳在基因组包装期间扩增，但保持结构稳定性。P74-26衣壳具有T = 7几何形状，尽管是嗜温同源物的两倍大。衣壳容量随着更大、更平坦的主要衣壳蛋白而增加。鉴于这些结果，我们预测降低二十面体复杂性（即T ≤ 7）会导致更稳定的衣壳组装。
The capsids of double-stranded DNA viruses protect the viral genome from the harsh extracellular environment, while maintaining stability against the high internal pressure of packaged DNA. To elucidate how capsids maintain stability in an extreme environment, we use cryoelectron microscopy to determine the capsid structure of thermostable phage P74-26 to 2.8-Å resolution. We find P74-26 capsids exhibit an overall architecture very similar to those of other tailed bacteriophages, allowing us to directly compare structures to derive the structural basis for enhanced stability. Our structure reveals lasso-like interactions that appear to function like catch bonds. This architecture allows the capsid to expand during genome packaging, yet maintain structural stability. The P74-26 capsid has T = 7 geometry despite being twice as large as mesophilic homologs. Capsid capacity is increased with a larger, flatter major capsid protein. Given these results, we predict decreased icosahedral complexity (i.e. T ≤ 7) leads to a more stable capsid assembly.