Negatively Charged Disordered Regions are Prevalent and Functionally Important Across Proteomes
Negatively Charged Disordered Regions are Prevalent and Functionally Important Across Proteomes
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DOI：
10.1016/j.jmb.2022.167660
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发表时间：
2022-06-10
影响因子：
5.6
通讯作者：
Levy, Yaakov
中科院分区：
文献类型：
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作者：
Bigman, Lavi S.;Iwahara, Junji;Levy, Yaakov
蛋白质的本质无序区(IDR)通常以高比例的带电残基为特征，但在它们的总净电荷和带电残基的组织方面不同。通过IDR费用构成和组织存储的功能编码信息仍然难以捉摸。在这里，我们的目标是通过对人、小鼠和酵母蛋白质组中IDRs的电荷性质进行全面的生物信息学分析来破译IDRs中的序列-功能关系。大约50%的蛋白质至少由一个带正电荷或带负电荷的IDR组成。与带正电荷的IDR相比，带负电荷的IDR更长，每个残基的净电荷更大。带正电荷的IDR和带负电荷的IDR之间的一个显著区别是重复单位的特征，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重复序列比K/R重复序列长约5倍，其中最长的包含49个残基。研究发现，在核酸相关蛋白中，较长的连续D和E片段更为普遍。它们在原核生物中不太常见，而在真核生物中，它们的丰度随着基因组大小的增加而增加。讨论了D/E重复的功能作用以及它们与K/R重复之间的深刻区别。(C)2022爱思唯尔有限公司版权所有。
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.(c) 2022 Elsevier Ltd. All rights reserved.