Physical motif clustering within intrinsically disordered nucleoporin sequences reveals universal functional features.

Physical motif clustering within intrinsically disordered nucleoporin sequences reveals universal functional features.
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DOI:
10.1371/journal.pone.0073831
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Gopinathan A
Gopinathan A
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Ando D;Colvin M;Rexach M;Gopinathan A

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考虑到同源蛋白的高突变率,并且其功能可能与序列不密切相关,无序蛋白的生物信息学尤其具有挑战性。在这里,我们进行了一种新的生物信息学分析,基于物理相关特征的空间聚类,如结合基序和无序蛋白质内的电荷,对数千种核孔复合物(NPC) FG基序含有蛋白质(FG nups)。FG蛋白调节核胞质运输的生物物理机制仍然难以捉摸。我们的分析揭示了单个FG序列结构中一系列高度保守的空间特征,如FG基序和蛋白链上带电残基的分离、定位和排序。这些功能保守的特征提供了对NPC核胞质运输调节的特定生物物理机制的深入了解,这强烈限制了当前的模型。此外,这种方法使我们能够在远亲物种中识别潜在功能类似的无序蛋白质。
Bioinformatics of disordered proteins is especially challenging given high mutation rates for homologous proteins and that functionality may not be strongly related to sequence. Here we have performed a novel bioinformatic analysis, based on the spatial clustering of physically relevant features such as binding motifs and charges within disordered proteins, on thousands of Nuclear Pore Complex (NPC) FG motif containing proteins (FG nups). The biophysical mechanism by which FG nups regulate nucleocytoplasmic transport has remained elusive. Our analysis revealed a set of highly conserved spatial features in the sequence structure of individual FG nups, such as the separation, localization, and ordering of FG motifs and charged residues along the protein chain. These functionally conserved features provide insight into the particular biophysical mechanisms responsible for regulation of nucleocytoplasmic traffic in the NPC, strongly constraining current models. Additionally this method allows us to identify potentially functionally analogous disordered proteins across distantly related species.
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