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

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.

SUBMITTER: Song Y

PROVIDER: S-EPMC5741666 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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

Song Youngzee Y Zhou Huihao H Vo My-Nuong MN Shi Yi Y Nawaz Mir Hussain MH Vargas-Rodriguez Oscar O Diedrich Jolene K JK Yates John R JR Kishi Shuji S Musier-Forsyth Karin K Schimmel Paul P

Nature communications 20171222 1

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 prol ...[more]

PMID: 29273753

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