Evolutionary rate heterogeneity in proteins with long disordered regions
Evolutionary rate heterogeneity in proteins with long disordered regions
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DOI：
10.1007/s00239-001-2309-6
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发表时间：
2002-07-01
影响因子：
3.9
通讯作者：
Dunker, AK
中科院分区：
文献类型：
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作者：
Brown, CJ;Takayama, S;Dunker, AK
蛋白质科学中的主流观点是三维（3-D）结构是蛋白质功能的先决条件。与这种主流观点相反，有许多反例蛋白质不能折叠成三维结构。或者有局部区域可以折叠，但仍能发挥功能。没有固定三维结构的蛋白质称为内在无序蛋白质。受无序蛋白质序列进化速率高于有序蛋白质序列进化速率的轶事报道的启发，我们将探索无序蛋白质的分子进化。为了测试无序蛋白质是否比有序蛋白质更快地进化，成对的遗传距离之间的有序和无序区域的26个蛋白质家族，至少有一个成员与结构特征的30个或更多个连续残基的无序区域进行了比较。对于五个家系，有序和无序序列之间的成对遗传距离没有显著差异。无序区域的发展速度显着高于有序区域的26个家庭的19。这些无序区域的功能是多样的，包括蛋白质、DNA或RNA的结合位点，还包括柔性接头。其中一些区域的功能尚不清楚。对于剩下的两个家族来说，无序区域的进化速度明显慢于有序区域。这些进化较慢的无序区域的功能包括DNA结合位点。需要更多的工作来了解内在有序和无序蛋白质进化速率差异的根本原因。
The dominant view in protein science is that a three-dimensional (3-D) structure is a prerequisite for protein function. In contrast to this dominant view, there are many counterexample proteins that fail to fold into a 3-D structure., or that have local regions that fall to fold, and yet carry out function. Protein without fixed 3-D structure is called intrinsically disordered. Motivated by anecdotal accounts of higher rates of sequence evolution in disordered protein than in ordered protein we Lire exploring the molecular evolution of disordered proteins. To test whether disordered protein evolves more rapidly than ordered protein, pairwise genetic distances were compared between the ordered and the disordered regions of 26 protein families having at least one member with a structurally characterized region of disorder of 30 or more consecutive residues. For five families, there were no significant differences in pairwise genetic distances between ordered and disordered sequences. The disordered region evolved significantly more rapidly than the ordered region for 19 of the 26 families. The functions of these disordered regions are diverse, including binding sites for protein, DNA, or RNA and also including flexible linkers. The functions of some of these regions are unknown. The disordered regions evolved significantly more slowly than the ordered regions for the two remaining families. The functions of these more slowly evolving disordered regions include sites for DNA binding. More work is needed to understand the underlying causes of the variability in the evolutionary rates of intrinsically ordered and disordered protein.