Negatively Charged Disordered Regions are Prevalent and Functionally Important Across Proteomes |
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Institution: | 1. Department of Chemical and Structural Biology, Weizmann Institute of Science, Rehovot, Israel;2. Department of Biochemistry and Molecular Biology, Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, TX 77555, United States;1. Department of Biochemistry & Molecular Biology, University of Chicago, Chicago, IL 60673, USA;1. Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA;1. Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts |
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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. |
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Keywords: | disordered regions repeat sequences D/E repeat polyampholytes electrostatics IDRs"} {"#name":"keyword" "$":{"id":"pc_1T7w1CPsBe"} "$$":[{"#name":"text" "_":"Intrinsically Disordered Regions NCPR"} {"#name":"keyword" "$":{"id":"pc_AWz7dGZMZk"} "$$":[{"#name":"text" "_":"Net Charge Per Residue NAR"} {"#name":"keyword" "$":{"id":"pc_cN1C3KpgJL"} "$$":[{"#name":"text" "_":"Nucleic Acid Related GO"} {"#name":"keyword" "$":{"id":"pc_EbjYpRNvIS"} "$$":[{"#name":"text" "_":"Gene Ontology |
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