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从基因表达谱洞察人类内在无序蛋白质。

Insights into human intrinsically disordered proteins from their gene expression profile.

作者信息

Panda Arup, Acharya Debarun, Chandra Ghosh Tapash

机构信息

Bioinformatics Centre, Bose Institute, P 1/12, C.I.T. Scheme VII M, Kolkata 700 054, West Bengal, India.

出版信息

Mol Biosyst. 2017 Nov 21;13(12):2521-2530. doi: 10.1039/c7mb00311k.

Abstract

Expression level provides important clues about gene function. Previously, various efforts have been undertaken to profile human genes according to their expression level. Intrinsically disordered proteins (IDPs) do not adopt any rigid conformation under physiological conditions, however, are considered as an important functional class in all domains of life. Based on a human tissue-averaged gene expression level, previous studies showed that IDPs are expressed at a lower level than ordered globular proteins. Here, we examined the gene expression pattern of human ordered and disordered proteins in 32 normal tissues. We noticed that in most of the tissues, ordered and disordered proteins are expressed at a similar level. Moreover, in a number of tissues IDPs were found to be expressed at a higher level than ordered proteins. Rigorous statistical analyses suggested that the lower tissue-averaged gene expression level of IDPs (reported earlier) may be the consequence of their biased gene expression in some specific tissues and higher protein length. When we considered the gene repertory of each tissue we noticed that a number of human tissues (brain, testes, etc.) selectively express a higher fraction of disordered proteins, which help them to maintain higher protein connectivity by forming disordered binding motifs and to sustain their functional specificities. Our results demonstrated that the disordered proteins are indispensable in these tissues for their functional advantages.

摘要

表达水平为基因功能提供了重要线索。此前,人们已开展了各种工作,根据人类基因的表达水平对其进行分析。内在无序蛋白(IDP)在生理条件下不具有任何刚性构象,然而,在生命的所有领域中,它们都被视为一类重要的功能蛋白。基于人类组织平均基因表达水平,先前的研究表明,IDP的表达水平低于有序的球状蛋白。在此,我们研究了32种正常组织中人类有序和无序蛋白的基因表达模式。我们注意到,在大多数组织中,有序和无序蛋白的表达水平相似。此外,在许多组织中,发现IDP的表达水平高于有序蛋白。严格的统计分析表明,IDP较低的组织平均基因表达水平(先前报道)可能是其在某些特定组织中基因表达存在偏差以及蛋白长度较长的结果。当我们考虑每个组织的基因库时,我们注意到许多人类组织(如大脑、睾丸等)选择性地表达更高比例的无序蛋白,这有助于它们通过形成无序结合基序来维持更高的蛋白连接性,并保持其功能特异性。我们的结果表明,无序蛋白因其功能优势在这些组织中不可或缺。

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