Intrinsic disorder in pathogenic and non-pathogenic microbes: discovering and analyzing the unfoldomes of early-branching eukaryotes
Intrinsic disorder in pathogenic and non-pathogenic microbes: discovering and analyzing the unfoldomes of early-branching eukaryotes
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DOI：
10.1039/b719168e
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发表时间：
2008-01-01
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：
Mohan, Amrita;Sullivan, William J., Jr.;Uversky, Vladimir N.
长期以来，寄生原生动物感染已被认为会导致人类和动物种群严重的疾病和死亡。尽管有注释的基因组的数量增加了大量的原生动物，还有很多关于他们的了解，从他们的基本生理过程中调用宿主-病原体相互作用的机制。这些基因组中的大多数都有一个共同的特征，即在其预测的蛋白质中低复杂性区域的高流行率，这被认为有助于在这个不同的早期分支真核生物群中个体物种的独特性。就引起疟疾的疟原虫物种而言，据报道这些区域也阻碍了同源物的鉴定，从而使功能基因组学变得异常具有挑战性。解释大量低复杂性区域的一个较好接受的理论是这些微生物中存在内在无序。在这项研究中，我们比较了预测在许多这样的古老真核细胞中表达的无序蛋白质的程度。我们的研究结果表明，一个不寻常的偏见的氨基酸组成的原生动物蛋白质组，并表明，内在的障碍是非常丰富的预测蛋白质。此外，在早期分支的真核生物中，内在无序的区域往往相当长。恶性疟原虫相互作用组的分析表明，蛋白质-蛋白质相互作用可能是内在疾病的至少一个功能。本研究为发现和分析早期分支真核生物的展开区（给定蛋白质组中内在无序蛋白质的互补）提供了生物信息学基础。它还为适应寄生生活方式的内在障碍的演变提供了新的见解，并为进一步研究该主题奠定了基础。
Parasitic protozoal infections have long been known to cause profound degrees of sickness and death in humans as well as animal populations. Despite the increase in the number of annotated genomes available for a large variety of protozoa, a great deal more has yet to be learned about them, from their fundamental physiology to mechanisms invoked during host-pathogen interactions. Most of these genomes share a common feature, namely a high prevalence of low complexity regions in their predicted proteins, which is believed to contribute to the uniqueness of the individual species within this diverse group of early-branching eukaryotes. In the case of Plasmodium species, which cause malaria, such regions have also been reported to hamper the identification of homologues, thus making functional genomics exceptionally challenging. One of the better accepted theories accounting for the high number of low complexity regions is the presence of intrinsic disorder in these microbes. In this study we compare the degree of disordered proteins that are predicted to be expressed in many such ancient eukaryotic cells. Our findings indicate an unusual bias in the amino acids comprising protozoal proteomes, and show that intrinsic disorder is remarkably abundant among their predicted proteins. Additionally, the intrinsically disordered regions tend to be considerably longer in the early-branching eukaryotes. An analysis of a Plasmodium falciparum interactome indicates that protein-protein interactions may be at least one function of the intrinsic disorder. This study provides a bioinfomatics basis for the discovery and analysis of unfoldomes ( the complement of intrinsically disordered proteins in a given proteome) of early-branching eukaryotes. It also provides new insights into the evolution of intrinsic disorder in the context of adapting to a parasitic lifestyle and lays the foundation for further work on the subject.