Double mimicry evades tRNA synthetase editing by toxic vegetable-sourced non-proteinogenic amino acid.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 29273753.
- Also identified by DOI 10.1038/s41467-017-02201-z and PMC identifier 5741666.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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.
Medical subject headings
- Alanine-tRNA Ligase
- Amino Acyl-tRNA Synthetases
- Azetidinecarboxylic Acid
- Cell Death
- Molecular Mimicry
- RNA, Transfer