Department of Chemical and Structural Biology, Weizmann Institute of Science, Rehovot, Israel. Electronic address: https://twitter.com/LaviBigman.
Department of Biochemistry and Molecular Biology, Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, TX 77555, United States.
J Mol Biol. 2022 Jul 30;434(14):167660. doi: 10.1016/j.jmb.2022.167660. Epub 2022 May 31.
Intrinsically disordered regions (IDRs) of proteins are often characterized by a high fraction of charged residues, but differ in their overall net charge and in the organization of the charged residues. The function-encoding information stored via IDR charge composition and organization remains elusive. Here, we aim to decipher the sequence-function relationship in IDRs by presenting a comprehensive bioinformatic analysis of the charge properties of IDRs in the human, mouse, and yeast proteomes. About 50% of the proteins comprise at least a single IDR, which is either positively or negatively charged. Highly negatively charged IDRs are longer and possess greater net charge per residue compared with highly positively charged IDRs. A striking difference between positively and negatively charged IDRs is the characteristics of the repeated units, specifically, of consecutive Lys or Arg residues (K/R repeats) and Asp or Glu (D/E repeats) residues. D/E repeats are found to be about five times longer than K/R repeats, with the longest found containing 49 residues. Long stretches of consecutive D and E are found to be more prevalent in nucleic acid-related proteins. They are less common in prokaryotes, and in eukaryotes their abundance increases with genome size. The functional role of D/E repeats and the profound differences between them and K/R repeats are discussed.
蛋白质的无规则区域（IDR）通常具有较高比例的带电残基，但它们的总净电荷和带电残基的组织方式不同。通过 IDR 电荷组成和组织存储的功能编码信息仍然难以捉摸。在这里，我们通过对人类、小鼠和酵母蛋白质组中 IDR 电荷特性进行全面的生物信息学分析，旨在破译 IDR 中的序列-功能关系。大约 50%的蛋白质至少包含一个正电荷或负电荷的 IDR。高度负电荷的 IDR 比高度正电荷的 IDR 更长，并且每个残基的净电荷更大。正电荷和负电荷 IDR 之间的一个显著区别是重复单元的特征，特别是连续的 Lys 或 Arg 残基（K/R 重复）和 Asp 或 Glu（D/E 重复）残基。D/E 重复比 K/R 重复长约五倍，最长的重复含有 49 个残基。连续的 D 和 E 长段在与核酸相关的蛋白质中更为常见。它们在原核生物中较少见，并且随着基因组大小的增加，在真核生物中的丰度增加。讨论了 D/E 重复的功能作用以及它们与 K/R 重复之间的深刻差异。
