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DOI10.1073/pnas.2001989117
Primordial emergence of a nucleic acid-binding protein via phase separation and statistical ornithine-to-arginine conversion
Longo L.M.; Despotović D.; Weil-Ktorza O.; Walker M.J.; Jabłońska J.; Fridmann-Sirkis Y.; Varani G.; Metanis N.; Tawfik D.S.
发表日期2020
ISSN0027-8424
起始页码15731
结束页码15739
卷号117期号:27
英文摘要De novo emergence demands a transition from disordered polypeptides into structured proteins with well-defined functions. However, can polypeptides confer functions of evolutionary relevance, and how might such polypeptides evolve into modern proteins? The earliest proteins present an even greater challenge, as they were likely based on abiotic, spontaneously synthesized amino acids. Here we asked whether a primordial function, such as nucleic acid binding, could emerge with ornithine, a basic amino acid that forms abiotically yet is absent in modern-day proteins. We combined ancestral sequence reconstruction and empiric deconstruction to unravel a gradual evolutionary trajectory leading from a polypeptide to a ubiquitous nucleic acid-binding protein. Intermediates along this trajectory comprise sequence-duplicated functional proteins built from 10 amino acid types, with ornithine as the only basic amino acid. Ornithine side chains were further modified into arginine by an abiotic chemical reaction, improving both structure and function. Along this trajectory, function evolved from phase separation with RNA (coacervates) to avid and specific double-stranded DNA binding. Our results suggest that phase-separating polypeptides may have been an evolutionary resource for the emergence of early proteins, and that ornithine, together with its postsynthesis modification to arginine, could have been the earliest basic amino acids. © 2020 National Academy of Sciences. All rights reserved.
英文关键词Abiotic amino acids; Helix-hairpin-helix; Prebiotic chemistry; Protein evolution; Protein synthesis
语种英语
scopus关键词arginine; double stranded DNA; nucleic acid binding protein; ornithine; amino acid; arginine; DNA; DNA binding protein; nucleoprotein; ornithine; peptide; protein; RNA; alpha helix; amino acid metabolism; amino acid sequence; amino acid substitution; amino acid synthesis; Article; binding affinity; coacervation; controlled study; phase separation; priority journal; protein DNA binding; protein folding; protein function; reaction analysis; structure activity relation; chemistry; genetics; Amino Acid Sequence; Amino Acids; Arginine; DNA; DNA-Binding Proteins; Nucleoproteins; Ornithine; Peptides; Proteins; RNA
来源期刊Proceedings of the National Academy of Sciences of the United States of America
文献类型期刊论文
条目标识符http://gcip.llas.ac.cn/handle/2XKMVOVA/158961
作者单位Longo, L.M., Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, 7610001, Israel; Despotović, D., Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, 7610001, Israel; Weil-Ktorza, O., Institute of Chemistry, Hebrew University of Jerusalem, Jerusalem, 9190401, Israel; Walker, M.J., Department of Chemistry, University of Washington, Seattle, WA 98195, United States; Jabłońska, J., Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, 7610001, Israel; Fridmann-Sirkis, Y., Life Sciences Core Facility, Weizmann Institute of Science, Rehovot, 7610001, Israel; Varani, G., Department of Chemistry, University of Washington, Seattle, WA 98195, United States; Metanis, N., Institute of Chemistry, Hebrew University of Jerusalem, Jerusalem, 9190401, Israel; Tawfik, D.S., Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, 7610001, Israel
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GB/T 7714
Longo L.M.,Despotović D.,Weil-Ktorza O.,et al. Primordial emergence of a nucleic acid-binding protein via phase separation and statistical ornithine-to-arginine conversion[J],2020,117(27).
APA Longo L.M..,Despotović D..,Weil-Ktorza O..,Walker M.J..,Jabłońska J..,...&Tawfik D.S..(2020).Primordial emergence of a nucleic acid-binding protein via phase separation and statistical ornithine-to-arginine conversion.Proceedings of the National Academy of Sciences of the United States of America,117(27).
MLA Longo L.M.,et al."Primordial emergence of a nucleic acid-binding protein via phase separation and statistical ornithine-to-arginine conversion".Proceedings of the National Academy of Sciences of the United States of America 117.27(2020).
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