Why do eukaryotic proteins contain more intrinsically disordered regions?
Why do eukaryotic proteins contain more intrinsically disordered regions?
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DOI：
10.1371/journal.pcbi.1007186
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发表时间：
2019-07-01
影响因子：
4.3
通讯作者：
Elofsson, Arne
中科院分区：
文献类型：
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作者：
Basile, Walter;Salvatore, Marco;Elofsson, Arne
与原核生物蛋白相比，内在疾病在真核化学中更丰富。预测内在疾病的方法基于蛋白质的氨基酸序列。因此，在真核和原核蛋白之间序列中必须存在潜在的差异，从而导致（预测）内在疾病的差异。通过比较蛋白质，从完整的真核和原核蛋白质组中进行比较，我们表明，内在障碍的差异来自连接PFAM结构域的接头区域。真核蛋白具有更多扩展的接头区域，此外，真核连接器的无序明显更高，38％vs. 12-16％的残留物。接下来，我们研究了真核接头障碍增加的根本原因，我们发现只有三个氨基酸的丰度变化会导致增加。真核蛋白含有8.6％的丝氨酸；虽然核酸蛋白含量为6.5％，但真核蛋白也含有5.4％的脯氨酸和5.3％的异亮氨酸蛋白，而原核生物中的脯氨酸为4.0％，近似于7.5％的异亮氨酸。这三个差异都导致真核蛋白的疾病增加。很容易推测，真核生物中丝氨酸频率的增加与激酶的调节有关，但缺乏直接的证据。在所有门，蛋白质家族，结构区域和蛋白质类型中都观察到差异，但在无序和接头区域中最为明显。观察到三种氨基酸的丰度差异会导致真核和原核蛋白之间的疾病差异引发了一个问题：真核连接器中的氨基酸频率是否有所不同，因为接头更加无序或差异会导致疾病增加？
Intrinsic disorder is more abundant in eukaryotic than prokaryotic proteins. Methods predicting intrinsic disorder are based on the amino acid sequence of a protein. Therefore, there must exist an underlying difference in the sequences between eukaryotic and prokaryotic proteins causing the (predicted) difference in intrinsic disorder. By comparing proteins, from complete eukaryotic and prokaryotic proteomes, we show that the difference in intrinsic disorder emerges from the linker regions connecting Pfam domains. Eukaryotic proteins have more extended linker regions, and in addition, the eukaryotic linkers are significantly more disordered, 38% vs. 12-16% disordered residues. Next, we examined the underlying reason for the increase in disorder in eukaryotic linkers, and we found that the changes in abundance of only three amino acids cause the increase. Eukaryotic proteins contain 8.6% serine; while prokaryotic proteins have 6.5%, eukaryotic proteins also contain 5.4% proline and 5.3% isoleucine compared with 4.0% proline and approximate to 7.5% isoleucine in the prokaryotes. All these three differences contribute to the increased disorder in eukaryotic proteins. It is tempting to speculate that the increase in serine frequencies in eukaryotes is related to regulation by kinases, but direct evidence for this is lacking. The differences are observed in all phyla, protein families, structural regions and type of protein but are most pronounced in disordered and linker regions. The observation that differences in the abundance of three amino acids cause the difference in disorder between eukaryotic and prokaryotic proteins raises the question: Are amino acid frequencies different in eukaryotic linkers because the linkers are more disordered or do the differences cause the increased disorder?