Comparing and combining predictors of mostly disordered proteins

Comparing and combining predictors of mostly disordered proteins
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DOI:
10.1021/bi047993o
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发表时间:
2005-02-15
期刊:
影响因子:
2.9
通讯作者:
Dunker, AK
Dunker, AK
中科院分区:
生物学3区
文献类型:
--
作者:
Oldfield, CJ;Cheng, Y;Dunker, AK

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内部无序的蛋白质和区域执行各种重要的细胞功能。具有无序区域的蛋白质在真核细胞中特别常见,其中这些蛋白质的子集大多是无序的,例如,无序的残基多于有序的残基先前已经描述了两种不同的方法,用于使用氨基酸序列来预测哪些蛋白质可能大部分是无序的。这些方法基于净电荷-亲水性分布和紊乱预测分数分布。每一种方法都被重新检验,并在此对预测结果进行了比较。提出了一种新的基于一致性的预测方法。将一致性方法应用于全基因组显示,大约4.5%的鼠疫耶尔森氏菌、5%的大肠杆菌K12、6%的闪烁古球菌、8%的热自养甲烷杆菌、23%的拟南芥和28%的小家鼠蛋白质大多是无序的。真核生物中大多数无序蛋白质的意外高频率对于大规模,高通量项目以及旨在确定蛋白质结构和功能的集中实验都具有重要意义。
Intrinsically disordered proteins and regions carry out varied and vital cellular functions. Proteins with disordered regions are especially common in eukaryotic cells, with a subset of these proteins being mostly disordered, e.g., with more disordered than ordered residues. Two distinct methods have been previously described for using amino acid sequences to predict which proteins are likely to be mostly disordered. These methods are based on the net charge-hydropathy distribution and disorder prediction score distribution. Each of these methods is reexamined, and the prediction results are compared herein. A new prediction method based on consensus is described. Application of the consensus method to whole genomes reveals that approximately 4.5% of Yersinia pestis, 5% of Escherichia coli K12, 6% of Archaeoglobus fulgidus, 8% of Methanobacterium thermoautotrophicum, 23% of Arabidopsis thaliana, and 28% of Mus musculus proteins are mostly disordered. The unexpectedly high frequency of mostly disordered proteins in eukaryotes has important implications both for large-scale, high-throughput projects and also for focused experiments aimed at determination of protein structure and function.