The intrinsic disorder status of the human hepatitis C virus proteome
The intrinsic disorder status of the human hepatitis C virus proteome
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DOI：
10.1039/c4mb00027g
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发表时间：
2014-01-01
影响因子：
--
通讯作者：
Uversky, Vladimir N.
中科院分区：
文献类型：
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作者：
Fan, Xiao;Xue, Bin;Uversky, Vladimir N.
许多病毒蛋白或其生物学重要区域整体上是无序的，或者包含长的无序区域。这些本质上无序的蛋白质/区域不具有独特的结构，并且具有补充“正常”有序蛋白质和结构域的功能库的功能，其中许多蛋白质功能类别严重依赖于内在的无序。病毒通常利用这些高度灵活的区域来入侵宿主生物体并劫持各种宿主系统。这些无序区域还帮助病毒适应其恶劣的栖息地并管理其对遗传物质的经济利用。在本文中，我们重点关注人类丙型肝炎病毒 (HCV) 蛋白质的结构特征，并使用广泛的生物信息学技术来评估几种人类 HCV 基因型的完整蛋白质组中内在紊乱的丰度，分析单个 HCV 蛋白质内紊乱分布的特征，并确定结构紊乱在十种 HCV 蛋白质功能中的潜在作用。我们表明，内在紊乱或增加的灵活性不仅在这些蛋白质中大量存在，而且对于它们的功能也是绝对必要的，在HCV多蛋白的蛋白水解加工、单个HCV蛋白质的成熟中发挥着至关重要的作用，并且与这些蛋白质的翻译后修饰及其与DNA、RNA和各种宿主蛋白质的相互作用有关。
Many viral proteins or their biologically important regions are disordered as a whole, or contain long disordered regions. These intrinsically disordered proteins/regions do not possess unique structures and possess functions that complement the functional repertoire of "normal" ordered proteins and domains, with many protein functional classes being heavily dependent on the intrinsic disorder. Viruses commonly use these highly flexible regions to invade the host organisms and to hijack various host systems. These disordered regions also help viruses in adapting to their hostile habitats and to manage their economic usage of genetic material. In this article, we focus on the structural peculiarities of proteins from human hepatitis C virus (HCV) and use a wide spectrum of bioinformatics techniques to evaluate the abundance of intrinsic disorder in the completed proteomes of several human HCV genotypes, to analyze the peculiarities of disorder distribution within the individual HCV proteins, and to establish potential roles of the structural disorder in functions of ten HCV proteins. We show that the intrinsic disorder or increased flexibility is not only abundant in these proteins, but is also absolutely necessary for their functions, playing a crucial role in the proteolytic processing of the HCV polyprotein, the maturation of the individual HCV proteins, and being related to the posttranslational modifications of these proteins and their interactions with DNA, RNA, and various host proteins.