A role for Z-DNA binding in vaccinia virus pathogenesis
A role for Z-DNA binding in vaccinia virus pathogenesis
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DOI：
10.1073/pnas.0431131100
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发表时间：
2003-06-10
影响因子：
11.1
通讯作者：
Rich, A
中科院分区：
文献类型：
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作者：
Kim, YG;Muralinath, M;Rich, A
牛痘病毒E3 L蛋白的N-末端结构域与具有确定的三维结构的Z-DNA结合蛋白家族具有序列相似性，并且其对于小鼠中的致病性是必需的。当其他Z-DNA结合结构域取代类似的E3 L结构域时，病毒在颅内接种后保持其致死性。在嵌合体中降低Z-DNA结合的突变与病毒致病性的降低相关，野生型E3 L中的类似突变也是如此。一种嵌合病毒，它含有一种不与Z-DNA结合的相关蛋白质，这种病毒是不致病的，但是一种产生Z-DNA结合的突变，就会产生一种致命的病毒。因此，结合Z构象的能力对于E31 L活性是必不可少的。这一发现可能允许设计一类抗病毒剂，包括抗天花（天花）的药物，其具有几乎相同的E3 L。
The N-terminal domain of the E3L protein of vaccinia virus has sequence similarity to a family of Z-DNA binding proteins of defined three-dimensional structure and it is necessary for pathogenicity in mice. When other Z-DNA-binding domains are substituted for the similar E3L domain, the virus retains its lethality after intracranial inoculation. Mutations decreasing Z-DNA binding in the chimera correlate with decreases in viral pathogenicity, as do analogous mutations in wild-type E3L. A chimeric virus incorporating a related protein that does not bind Z-DNA is not pathogenic, but a mutation that creates Z-DNA binding makes a lethal virus. The ability to bind the Z conformation is thus essential to E31L activity. This finding may allow the design of a class of antiviral agents, including agents against variola (smallpox), which has an almost identical E3L.