Intrinsically disordered loops inserted into the structural domains of human proteins
Intrinsically disordered loops inserted into the structural domains of human proteins
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DOI：
10.1016/j.jmb.2005.10.037
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发表时间：
2006-01-27
影响因子：
5.6
通讯作者：
Nishikawa, K
中科院分区：
文献类型：
--
作者：
Fukuchi, S;Homma, K;Nishikawa, K
结构部分或完全无序的蛋白质是近年来研究的热点之一，它们广泛存在于真核生物中，主要参与转录调控、翻译和细胞信号转导等重要的细胞生物学过程。长的无序序列有时插入蛋白质的单一结构域中，从分子表面形成环。这种内在无序环（IDL）在X射线晶体学中是不可见的，或者由于极大的灵活性而阻碍蛋白质结晶本身。也许正因为如此，这样长的无序序列还没有得到充分的表征。在这里，我们提出了一个信息的方法，严格识别IDLs的结构域的蛋白质单独使用的氨基酸序列。使用该方法进行的人类蛋白质全基因组调查确定了50种含IDL的蛋白质，其中几种已经通过实验确定了3D结构。在其他完全测序的生物体中进行的类似搜索显示，IDL在真核生物中普遍存在，而在原核生物中则少得多。由于在真核生物中，IDLs的边界和外显子的边界在统计学上有显著的一致性，我们认为IDLs主要是通过外显子添加产生的。IDL几乎总是位于蛋白质的表面并且富含亲水性残基，并且含有IDL的蛋白质倾向于在细胞内。一些充分表征的具有IDL的蛋白质说明IDL在细胞内信号传导或调节功能的切换中起关键作用，这表明IDL插入是产生功能不同的结构域变体的有效方式。(c)2005爱思唯尔有限公司保留所有权利。
Much attention has been paid recently to proteins with partially or fully disordered structures, which are found to exist mostly in eukaryotes and are involved mainly in pivotal cellular processes such as transcriptional regulation, translation and cellular signal transduction. Long disordered sequences are sometimes inserted within the single structural domains of proteins, forming loops from the molecular surface. Such intrinsically disordered loops (IDLs) either are invisible in X-ray crystallography, or hamper protein crystallization itself due to great flexibility. Perhaps because of this, such long disordered sequences have not been characterized adequately. Here, we propose an informational method that stringently identifies IDLs in the structural domains of proteins using the amino acid sequence alone. A genome-wide survey of human proteins conducted with the method identified 50 IDL-containing proteins, several of which have experimentally determined 3D structures. Similar searches in other entirely sequenced organisms revealed that IDLs are prevalent in eukaryotes, while they are much less so in prokaryotes. As there is a statistically significant coincidence between the boundaries of TDLs and those of exons, we suggest that IDLs were produced mainly by exon addition in eukaryotes. IDLs are almost always located at the surface of proteins and are enriched with hydrophilic residues, and IDL-containing proteins tend to be intracellular. Some of the well-characterized proteins with IDLs illustrate that IDLs play pivotal roles in the switching of intracellular signaling or regulatory functions, suggesting that IDL insertion is an effective way to create functionally different domain variants. (c) 2005 Elsevier Ltd. All rights reserved.