Double mimicry evades tRNA synthetase editing by toxic vegetable-sourced non-proteinogenic amino acid

Nat Commun. 2017 Dec 22;8(1):2281. doi: 10.1038/s41467-017-02201-z.


Hundreds of non-proteinogenic (np) amino acids (AA) are found in plants and can in principle enter human protein synthesis through foods. While aminoacyl-tRNA synthetase (AARS) editing potentially provides a mechanism to reject np AAs, some have pathological associations. Co-crystal structures show that vegetable-sourced azetidine-2-carboxylic acid (Aze), a dual mimic of proline and alanine, is activated by both human prolyl- and alanyl-tRNA synthetases. However, it inserts into proteins as proline, with toxic consequences in vivo. Thus, dual mimicry increases odds for mistranslation through evasion of one but not both tRNA synthetase editing systems.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alanine
  • Alanine-tRNA Ligase / metabolism*
  • Amino Acids
  • Amino Acyl-tRNA Synthetases / metabolism*
  • Azetidinecarboxylic Acid / metabolism*
  • Cell Death*
  • HeLa Cells
  • Humans
  • Molecular Mimicry*
  • Proline
  • Protein Biosynthesis
  • RNA Editing
  • RNA, Transfer / metabolism*
  • Vegetables


  • Amino Acids
  • Azetidinecarboxylic Acid
  • RNA, Transfer
  • Proline
  • Amino Acyl-tRNA Synthetases
  • prolyl T RNA synthetase
  • Alanine-tRNA Ligase
  • Alanine