Naslov
What shaped selectivity of the class I editing domain?

Autori
Gruic-Sovulj, Ita

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

Izvornik
12th International Symposium on Aminoacyl-tRNA Symthetases / Min-Xin Guan - , 2019, 18-18

Skup
12th International Symposium on Aminoacyl-tRNA Symthetases

Mjesto i datum
Hangzhou, Kina, 05.11.2019. - 09.11.2019

Vrsta sudjelovanja
Pozvano predavanje

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
aminoacyl-tRNA synthetases, post-transfer editing, norvaline, synthetic amino acids

Sažetak
The mechanisms that govern amino acid selectivity in AARS synthetic sites are well established. However, what shaped the selectivity of the post- transfer editing domain has been less clear. The double sieve hypothesis suggests that the editing site evolved primarily to edit smaller non- cognate amino acids that are poorly discriminate against at the synthetic site. We have recently shown that the non-proteinogenic α-aminobutyrate (Abu) and its unnatural fluorinated analogues are efficiently discriminated at the Escherichia coli IleRS synthetic site but are still rapidly cleared by the editing domain. Thus, the editing domain seems to display broad specificity, also hydrolyzing amino acids that are efficiently discriminated by the synthetic site. We also found that a prime substrate of LeuRS post- transfer editing is non-proteinogenic norvaline (Nva). Furthermore, IleRS exhibited more efficient editing of Nva relative to Val, in agreement with our finding that Nva misicorporation at Ile positions is more toxic than Val-to-Ile substitution. Finally, ValRS also rapidly hydrolyzed Nva-tRNAVal even though Nva is efficiently discriminated at the synthetic site. Is this a coincidence ; or may be related to IleRS, LeuRS and ValRS being evolutionarily related and also sharing an editing domain of common origin? Overall, our findings suggest a more complex model than the double sieve, and provoke an intriguing question – did the last common ancestor of IleRS, LeuRS and ValRS acquire the editing domain mainly to prevent Nva (and Abu) incorporation at the dawn of modern translation?

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Biologija

POVEZANOST RADA