Negatively Charged Disordered Regions are Prevalent and Functionally Important Across Proteomes. Issue 14 (30th July 2022)

• Record Type: Journal Article
• Authors: Bigman, Lavi S.; Iwahara, Junji; Levy, Yaakov
• Is Part Of: Journal of molecular biology. Volume 434:Issue 14(2022)
• Publication Date: 2022-07-30
• Subjects: disordered regions -- repeat sequences -- D/E repeat -- polyampholytes -- electrostatics; IDRs Intrinsically Disordered Regions -- NCPR Net Charge Per Residue -- NAR Nucleic Acid Related -- GO Gene Ontology; Molecular biology -- Periodicals; Biology -- Periodicals; Biochemistry -- Periodicals; Bacteriology -- Periodicals; Molecular Biology -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biologie -- Périodiques; Biochimie -- Périodiques; Moleculaire biologie; Biochemistry; Biology; Molecular biology; Periodicals; 572.805
• DOI: 10.1016/j.jmb.2022.167660
• Languages: English
• ISSNs: 0022-2836

Abstract

Graphical abstract: Highlights: Intrinsically disordered regions in proteins are often highly charged and have polyampholytic characteristics. In many other cases, the disordered regions are of polyelectrolytic nature due to long repeats of positive or negative residues. We found that highly negatively charged disordered regions are much more common than highly positively charged tails. D/E repeats in proteins are much longer than K/R repeats and are more common in nucleic acids related proteins. The abundance of long D/E repeats increases with genome size. Abstract: 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.