Rapid evolution exposes the boundaries of domain structure and function in natively unfolded FG nucleoporins
Rapid evolution exposes the boundaries of domain structure and function in natively unfolded FG nucleoporins
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DOI：
10.1074/mcp.m600309-mcp200
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发表时间：
2007-02-01
影响因子：
7
通讯作者：
Rexach, Michael F.
中科院分区：
文献类型：
--
作者：
Denning, Daniel P.;Rexach, Michael F.
具有苯丙氨酸-甘氨酸重复序列（FG Nups）的核孔蛋白在核孔复合物（NPC）处起促进核质转运的作用。在酿酒酵母中，每个FG Nup含有一个大的天然未折叠结构域，该结构域被FG重复序列打断。这些FG重复序列被无序蛋白质结构域常见的亲水性氨基酸（AA）包围。在这里，我们表明，FG结构域的Nups从人类，苍蝇，蠕虫，和其他酵母物种也丰富了这些疾病相关的氨基酸，表明结构紊乱是一个保守的功能FG Nups和可能在NPC功能中发挥重要作用。尽管AA组成保守，但来自不同物种的FIG Nup序列显示出广泛的分歧。在四个酵母属物种中具有同线直系同源物的蛋白质的AA取代率的比较揭示，FG Nup以平均酵母蛋白质的两倍的速率进化，其中大多数取代发生在FIG重复序列之间的序列中。FG NUPS的快速进化是很难解释的参数已知的影响AA取代率，如蛋白质表达水平，交互性，和必要性，而不是他们的快速进化可能反映了一个内在的宽容的天然展开的结构AA取代。FG Nups中AA序列保守性的总体缺乏与保守序列的离散延伸形成鲜明对比。这些保守的序列突出了已知的核转运蛋白和核孔蛋白结合位点以及其他可能具有重要结构和功能特性的未知位点。
Nucleoporins with phenylalanine-glycine repeats (FG Nups) function at the nuclear pore complex (NPC) to facilitate nucleocytoplasmic transport. In Saccharomyces cerevisiae, each FG Nup contains a large natively unfolded domain that is punctuated by FG repeats. These FG repeats are surrounded by hydrophilic amino acids (AAs) common to disordered protein domains. Here we show that the FG domain of Nups from human, fly, worm, and other yeast species is also enriched in these disorder-associated AAs, indicating that structural disorder is a conserved feature of FG Nups and likely serves an important role in NPC function. Despite the conservation of AA composition, FIG Nup sequences from different species show extensive divergence. A comparison of the AA substitution rates of proteins with syntenic orthologs in four Saccharomyces species revealed that FG Nups have evolved at twice the rate of average yeast proteins with most substitutions occurring in sequences between FIG repeats. The rapid evolution of FG Nups is poorly explained by parameters known to influence AA substitution rate, such as protein expression level, interactivity, and essentiality; instead their rapid evolution may reflect an intrinsic permissiveness of natively unfolded structures to AA substitutions. The overall lack of AA sequence conservation in FG Nups is sharply contrasted by discrete stretches of conserved sequences. These conserved sequences highlight known karyopherin and nucleoporin binding sites as well as other uncharacterized sites that may have important structural and functional properties.