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首页> 外文期刊>The FEBS journal >Japanese encephalitis virus - exploring the dark proteome and disorder-function paradigm
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Japanese encephalitis virus - exploring the dark proteome and disorder-function paradigm

机译：日本脑炎病毒 - 探索黑暗蛋白质组和无序函数范式

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Japanese encephalitis virus (JEV) is one of the major causes of viral encephalitis all around the globe. Approximately 3 billion people in endemic areas are at risk of Japanese encephalitis. To develop a wholistic understanding of the viral proteome, it is important to investigate both its ordered and disordered proteins. However, the functional and structural significance of disordered regions in the JEV proteome has not been systematically investigated as of yet. To fill this gap, we used here a set of bioinformatics tools to analyze the JEV proteome for the predisposition of its proteins for intrinsic disorder and for the presence of the disorder-based binding regions (also known as molecular recognition features, MoRFs). We also analyzed all JEV proteins for the presence of the probable nucleic acid-binding (DNA and RNA) sites. The results of these computational studies are experimentally validated using JEV capsid protein as an illustrative example. In agreement with bioinformatic analysis, we found that the N-terminal region of the JEV capsid (residues 1-30) is intrinsically disordered. We showed that this region is characterized by the temperature response typical for highly disordered proteins. Furthermore, we have experimentally shown that this disordered N-terminal domain of a capsid protein has a noticeable 'gain-of-structure' potential. In addition, using DOPS liposomes, we demonstrated the presence of pronounced membrane-mediated conformational changes in the N-terminal region of JEV capsid. In our view, this disorder-centric analysis would be helpful for a better understanding of the JEV pathogenesis.
机译：日本脑炎病毒（JEV）是全球病毒脑炎的主要原因之一。地方性区域约有30亿人面临日本脑炎的风险。为了制定对病毒蛋白质组的更新理解，重要的是研究其有序和无序的蛋白质。然而，JEV蛋白质组中无序区域的功能和结构性显着性尚未得到系统地研究。为了填补这种差距，我们在这里使用了一组生物信息学工具，用于分析其蛋白质的JEV蛋白质，用于内在疾病，并且存在基于病症的结合区域（也称为分子识别特征，Morfs）。我们还分析了所有JEV蛋白的存在，用于存在可能的核酸结合（DNA和RNA）位点。这些计算研究的结果使用JEV Capsid蛋白作为说明性实例进行了实验验证。在与生物信息分析的同意中，我们发现JEV衣壳的N-末端区域（残留物1-30）是本质无序的。我们认为该地区的特征在于典型的温度响应对高紊乱的蛋白质。此外，我们已经通过实验证明了衣壳蛋白的这种无序的N-末端结构域具有显着的“结构增益”潜力。另外，使用DOPS脂质体，我们证明了JEV Capsid的N-末端区域中明显的膜介导的构象变化。在我们看来，这种障碍为中心的分析对于更好地了解JEV发病机制有助于。

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