Intrinsically disordered proteins (IDPs) are an important class of proteins in all domains of life for their functional importance. However, how nature has shaped the disorder potential of prokaryotic and eukaryotic proteins is still not clearly known. Randomly generated sequences are free of any selective constraints, thus these sequences are commonly used as null models. Considering different types of random protein models, here we seek to understand how the disorder potential of natural eukaryotic and prokaryotic proteins differs from random sequences. Comparing proteome-wide disorder content between real and random sequences of 12 model organisms, we noticed that eukaryotic proteins are enriched in disordered regions compared to random sequences, but in prokaryotes such regions are depleted. By analyzing the position-wise disorder profile, we show that there is a generally higher disorder near the N- and C-terminal regions of eukaryotic proteins as compared to the random models; however, either no or a weak such trend was found in prokaryotic proteins. Moreover, here we show that this preference is not caused by the amino acid or nucleotide composition at the respective sites. Instead, these regions were found to be endowed with a higher fraction of protein–protein binding sites, suggesting their functional importance. We discuss several possible explanations for this pattern, such as improving the efficiency of protein–protein interaction, ribosome movement during translation, and post-translational modification. However, further studies are needed to clearly understand the biophysical mechanisms causing the trend.

内在无序的蛋白质(IDP) 是生命所有领域中的一类重要蛋白质，因为它们具有功能重要性。然而，自然界如何塑造原核和真核蛋白质的紊乱潜力仍不清楚。随机生成的序列不受任何选择性约束，因此这些序列通常用作空模型。考虑到不同类型的随机蛋白质模型，在这里我们试图了解天然真核和原核蛋白质的无序潜力与随机序列有何不同。比较 12 个模型生物的真实和随机序列之间的蛋白质组范围内的无序内容，我们注意到与随机序列相比，真核蛋白质在无序区域中富集，但在原核生物中这些区域被耗尽。通过分析位置无序分布，我们表明，与随机模型相比，真核蛋白质的 N 和 C 末端区域附近通常存在更高的紊乱；然而，在原核蛋白质中没有发现或没有发现这种趋势。此外，我们在这里表明这种偏好不是由相应位点的氨基酸或核苷酸组成引起的。相反，发现这些区域具有更高比例的蛋白质 - 蛋白质结合位点，表明它们的功能重要性。我们讨论了这种模式的几种可能解释，例如提高蛋白质-蛋白质相互作用的效率、翻译过程中的核糖体运动和翻译后修饰 在原核蛋白质中没有发现或没有发现这种趋势。此外，我们在这里表明这种偏好不是由相应位点的氨基酸或核苷酸组成引起的。相反，发现这些区域具有更高比例的蛋白质 - 蛋白质结合位点，表明它们的功能重要性。我们讨论了这种模式的几种可能解释，例如提高蛋白质-蛋白质相互作用的效率、翻译过程中的核糖体运动和翻译后修饰 在原核蛋白质中没有发现或没有发现这种趋势。此外，我们在这里表明这种偏好不是由相应位点的氨基酸或核苷酸组成引起的。相反，发现这些区域具有更高比例的蛋白质 - 蛋白质结合位点，表明它们的功能重要性。我们讨论了这种模式的几种可能解释，例如提高蛋白质-蛋白质相互作用的效率、翻译过程中的核糖体运动和翻译后修饰. 然而，需要进一步的研究来清楚地了解导致这种趋势的生物物理机制。