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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >White Spot Syndrome Virus Protein Icp11:a Histone-binding Dna Mimic That Disrupts Nucleosome Assembly
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White Spot Syndrome Virus Protein Icp11:a Histone-binding Dna Mimic That Disrupts Nucleosome Assembly

机译:白斑综合症病毒蛋白Icp11:组蛋白结合的Dna模仿物破坏了核小体的组装。

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摘要

White spot syndrome virus (WSSV) is a large (≈300 kbp), double-stranded DNA eukaryotic virus that has caused serious disease in crustaceans worldwide. ICP11 is the most highly expressed WSSV nonstructural gene/protein, which strongly suggests its importance in WSSV infection; but until now, its function has remained obscure. We show here that ICP11 acts as a DNA mimic. In crystal, ICP11 formed a polymer of dimers with 2 rows of negatively charged spots that approximated the duplex arrangement of the phosphate groups in DNA. Functionally, ICP11 prevented DNA from binding to histone proteins H2A, H2B, H3, and H2A.x, and in hemocytes from WSSV-infected shrimp, ICP11 colocalized with histone H3 and activated-H2A.x. These observations together suggest that ICP11 might interfere with nucleosome assembly and prevent H2A.x from fulfilling its critical function of repairing DNA double strand breaks. Therefore, ICP11 possesses a functionality that is unique among the handful of presently known DNA mimic proteins.
机译:白斑综合症病毒(WSSV)是一种大型(≈300kbp)双链DNA真核病毒,已在全世界甲壳类动物中引起严重疾病。 ICP11是表达最高的WSSV非结构基因/蛋白质,强烈表明其在WSSV感染中的重要性。但是直到现在,它的功能仍然不清楚。我们在这里显示ICP11充当DNA模拟物。在晶体中,ICP11形成了具有2行带负电荷斑点的二聚体聚合物,该行带有近似于DNA中磷酸基团的双链排列。在功能上,ICP11阻止DNA与组蛋白H2A,H2B,H3和H2A.x结合,在WSSV感染虾的血细胞中,ICP11与组蛋白H3和活化的H2A.x共定位。这些观察结果共同表明,ICP11可能会干扰核小体的组装并阻止H2A.x发挥其修复DNA双链断裂的关键功能。因此,ICP11具有在目前已知的少数几种DNA模拟蛋白中独有的功能。

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