Reconstruction and Characterization of Thermally Stable and Catalytically Active Proteins Comprising an Alphabet of ~ 13 Amino Acids

Madoka Kimura, Satoshi Akanuma*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

While extant organisms synthesize proteins using approximately 20 kinds of genetically coded amino acids, the earliest protein synthesis system is likely to have been much simpler, utilizing a reduced set of amino acids. However, which types of building blocks were involved in primordial protein synthesis remains unclear. Herein, we reconstructed three convergent sequences of an ancestral nucleoside diphosphate kinase, each comprising a 10 amino acid “alphabet,” and found that two of these variants folded into soluble and stable tertiary structures. Therefore, an alphabet consisting of 10 amino acids contains sufficient information for creating stable proteins. Furthermore, re-incorporation of a few more amino acid types into the active site of the 10 amino acid variants improved the catalytic activity, although the specific activity was not as high as that of extant proteins. Collectively, our results provide experimental support for the idea that robust protein scaffolds can be built with a subset of the current 20 amino acids that might have existed abundantly in the prebiotic environment, while the other amino acids, especially those with functional sidechains, evolved to contribute to efficient enzyme catalysis.

Original languageEnglish
Pages (from-to)372-381
Number of pages10
JournalJournal of Molecular Evolution
Volume88
Issue number4
DOIs
Publication statusPublished - 2020 May 1

Keywords

  • Amino acid usage
  • Origin of life
  • Prebiotic amino acids
  • Primordial protein
  • Reduced amino acid set
  • Stable tertiary structure

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics

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