Major capsid reinforcement by a minor protein in herpesviruses and phage.

Major capsid reinforcement by a minor protein in herpesviruses and phage.
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在疱疹病毒和噬菌体中,次要蛋白质的主要衣壳加固。

DOI:
10.1093/nar/gku634
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发表时间:
2014-08
影响因子:
14.9
通讯作者:
Evilevitch A
Evilevitch A
中科院分区:
生物学2区
文献类型:
--
作者:
Sae-Ueng U;Liu T;Catalano CE;Huffman JB;Homa FL;Evilevitch A

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单纯疱疹病毒1型(HSV-1)和噬菌体λ衣壳在自组装和DNA包装过程中经历了相当大的结构变化。病毒衣壳自组装的初始步骤需要衣壳亚基之间存在弱的非共价相互作用,以确保自由能最小化和无错误组装。然而,在DNA包装的最后阶段,内部基因组压力急剧增加,需要显著的衣壳强度来承受数十个大气压的高内部基因组压力。我们的数据显示,松散形成的衣壳结构在组装后被HSV-1中的次要衣壳蛋白UL 25和λ噬菌体中的gpD增强。使用原子力显微镜纳米压痕分析,我们表明,由于增加的结构稳定性的结合UL 25和gpD的衣壳变得更硬。同时,对于疱疹病毒和噬菌体,破坏衣壳所需的力增加了70%。这证明了次要衣壳蛋白的普遍和进化上保守的功能:促进加压的病毒基因组在衣壳中的保留。由于所有八种人类疱疹病毒都具有UL 25直系同源物,这一发现提供了通过破坏对病毒复制至关重要的衣壳化DNA和衣壳蛋白之间的精确力平衡来干扰疱疹复制的新机会。
Herpes simplex type 1 virus (HSV-1) and bacteriophage λ capsids undergo considerable structural changes during self-assembly and DNA packaging. The initial steps of viral capsid self-assembly require weak, non-covalent interactions between the capsid subunits to ensure free energy minimization and error-free assembly. In the final stages of DNA packaging, however, the internal genome pressure dramatically increases, requiring significant capsid strength to withstand high internal genome pressures of tens of atmospheres. Our data reveal that the loosely formed capsid structure is reinforced post-assembly by the minor capsid protein UL25 in HSV-1 and gpD in bacteriophage λ. Using atomic force microscopy nano-indentation analysis, we show that the capsid becomes stiffer upon binding of UL25 and gpD due to increased structural stability. At the same time the force required to break the capsid increases by ∼70% for both herpes and phage. This demonstrates a universal and evolutionarily conserved function of the minor capsid protein: facilitating the retention of the pressurized viral genome in the capsid. Since all eight human herpesviruses have UL25 orthologs, this discovery offers new opportunities to interfere with herpes replication by disrupting the precise force balance between the encapsidated DNA and the capsid proteins crucial for viral replication.
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