Naslov
Trimming a branch: norvaline is more toxic than valine in isoleucine mistranslation

Autori
Biluš, Mirna ; Šemanjski, Maja ; Močibob, Marko ; Živković, Igor ; Cvetešić, Nevena ; Tawfik, Dan ; Toth-Petroczy, Agnes ; Gruić-Sovulj, Ita

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
3rd International Conference on Post-Translational Modifications in Bacteria / - Tübingen, 2018, 33-33

Skup
3rd International Conference on Post-Translational Modifications in Bacteria

Mjesto i datum
Tübingen, Njemačka, 03.12.2018. - 04.12.2018

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
isoleucyl-tRNA synthetases, norvaline, mistranslation, editing

Sažetak
The genetic code is virtually universal in biology. The extent to which mistranslation occurs is still poorly understood and presents a fundamental question in basic research and production of recombinant proteins. Translational errors are partly prevented by the editing activity of aminoacyl-tRNA synthetases (aaRSs), the enzymes that couple the cognate pair of amino acid and tRNA for ribosomal protein synthesis. Norvaline (Nva) is a linear side-chain non- proteinogenic amino acid which sporadically accumulates in cells. Comparing Nva to Val, which is proteinogenic, beta-branched amino acid of the same mass, in their ability to mimic Ile in translation is intriguing. We showed that, both in vitro and in vivo, Nva and Val are equally good non-cognate substrates of the IleRS mutant lacking a functional editing domain. In contrast, IleRS appears to have more efficient editing against Nva than against Val. Accordingly, we found that incorporation of Nva into the Escherichia coli proteome is more deleterious, although Nva is mistranslated with similar frequency to Val and largely at the same Ile positions. Comparison of Nva-tRNA editing by IleRS, LeuRS and ValRS suggests that Nva editing was present in their common ancestor, prior to its duplication and divergence to three specialized enzymes. This raises an intriguing hypothesis that Nva may had participated in primordial translation.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Biologija

POVEZANOST RADA