Genome-scale identification and characterization of moonlighting proteins.
Genome-scale identification and characterization of moonlighting proteins.
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DOI：
10.1186/s13062-014-0030-9
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发表时间：
2014-12-11
期刊：
影响因子：
5.5
通讯作者：
Kihara D
中科院分区：
文献类型：
--
作者：
Khan I;Chen Y;Dong T;Hong X;Takeuchi R;Mori H;Kihara D
月光蛋白执行两种或多种细胞功能，这些功能是根据不同的环境选择的，包括它们表达的细胞类型、它们的寡聚化状态以及不同位点上不同配体的结合。为了了解其功能多样性的整体情况，建立能够以系统的方式识别兼职蛋白质的方法是很重要的。在这里，我们开发了一个计算框架，在基因组尺度上寻找兼职蛋白质，并确定了这些蛋白质的多个蛋白质组学特征。首先，我们分析了已知兼职蛋白的基因本体（GO）注释。我们发现月光蛋白的GO注释可以聚集成多个组，反映了它们的不同功能。然后，结合观察到的氧化石墨烯项分离，我们在大肠杆菌中鉴定出33种新的月光蛋白，并通过文献复习加以证实。接下来，我们从蛋白质相互作用、基因表达、系统发育特征和基因相互作用网络等方面分析了兼职蛋白。我们发现，与非兼职蛋白质相比，兼职蛋白质与更多不同功能类别的蛋白质进行物理相互作用，并且还发现兼职蛋白质的大多数物理相互作用伙伴共享后者的主要功能。有趣的是，我们还发现兼职蛋白倾向于与其他兼职蛋白相互作用。在基因表达和系统发育相关蛋白方面，观察到一个微弱的趋势，即兼职蛋白与功能更多样化的蛋白相互作用。研究了月光蛋白的结构特征，即内在无序区和配体结合位点。兼职蛋白的附加功能难以通过实验确定，这些蛋白质也对计算功能注释提出了重大挑战。我们的方法能够从公共数据库中当前的功能注释中识别出新的兼职蛋白。此外，我们表明，没有足够功能注释的潜在兼职蛋白可以通过分析现有的组学规模数据来识别。我们的发现为在系统水平上研究蛋白质的多功能性质以及探索细胞中蛋白质的复杂功能相互作用开辟了新的可能性。本文由Michael Galperin， Eugine Koonin和Nick Grishin审阅。本文的在线版本（doi:10.1186/s13062-014-0030-9）包含补充资料，仅供授权用户使用。
Moonlighting proteins perform two or more cellular functions, which are selected based on various contexts including the cell type they are expressed, their oligomerization status, and the binding of different ligands at different sites. To understand overall landscape of their functional diversity, it is important to establish methods that can identify moonlighting proteins in a systematic fashion. Here, we have developed a computational framework to find moonlighting proteins on a genome scale and identified multiple proteomic characteristics of these proteins. First, we analyzed Gene Ontology (GO) annotations of known moonlighting proteins. We found that the GO annotations of moonlighting proteins can be clustered into multiple groups reflecting their diverse functions. Then, by considering the observed GO term separations, we identified 33 novel moonlighting proteins in Escherichia coli and confirmed them by literature review. Next, we analyzed moonlighting proteins in terms of protein-protein interaction, gene expression, phylogenetic profile, and genetic interaction networks. We found that moonlighting proteins physically interact with a higher number of distinct functional classes of proteins than non-moonlighting ones and also found that most of the physically interacting partners of moonlighting proteins share the latter’s primary functions. Interestingly, we also found that moonlighting proteins tend to interact with other moonlighting proteins. In terms of gene expression and phylogenetically related proteins, a weak trend was observed that moonlighting proteins interact with more functionally diverse proteins. Structural characteristics of moonlighting proteins, i.e. intrinsic disordered regions and ligand binding sites were also investigated. Additional functions of moonlighting proteins are difficult to identify by experiments and these proteins also pose a significant challenge for computational function annotation. Our method enables identification of novel moonlighting proteins from current functional annotations in public databases. Moreover, we showed that potential moonlighting proteins without sufficient functional annotations can be identified by analyzing available omics-scale data. Our findings open up new possibilities for investigating the multi-functional nature of proteins at the systems level and for exploring the complex functional interplay of proteins in a cell. This article was reviewed by Michael Galperin, Eugine Koonin, and Nick Grishin. The online version of this article (doi:10.1186/s13062-014-0030-9) contains supplementary material, which is available to authorized users.
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