Naslov
On the Mechanism and Origin of Isoleucyl-tRNA Synthetase Editing against Norvaline

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

Izvornik
Journal of molecular biology (0022-2836) 431 (2019), 6; 1284-1297

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
aminoacyl-tRNA synthetase ; mistranslation ; proofreading ; non-proteinogenic amino acids ; primordial translation

Sažetak
Aminoacyl-tRNA synthetases (aaRSs), the enzymes responsible for coupling tRNAs to their cognate amino acids, minimize translational errors by intrinsic hydrolytic editing. Here, we compared norvaline (Nva), a linear amino acid not coded for protein synthesis, to the proteinogenic, branched valine (Val) in their propensity to mistranslate isoleucine (Ile) in proteins. We show that in the synthetic site of isoleucyl- tRNA synthetase (IleRS), Nva and Val are activated and transferred to tRNA at similar rates. The efficiency of the synthetic site in pre-transfer editing of Nva and Val also appears to be similar. Post-transfer editing was, however, more rapid with Nva and consequently IleRS misaminoacylates Nva- tRNA(Ile) at slower rate than Val-tRNA(Ile). Accordingly, an Escherichia coli strain lacking IleRS post-transfer editing misincorporated Nva and Val in the proteome to a similar extent and at the same Ile positions. However, Nva mistranslation inflicted higher toxicity than Val, in agreement with IleRS editing being optimized for hydrolysis of Nva-tRNA(Ile). Furthermore, we found that the evolutionary- related IleRS, leucyl- and valyl-tRNA synthetases (I/L/VRSs), all efficiently hydrolyze Nva-tRNAs even when editing of Nva seems redundant. We thus hypothesize that editing of Nva-tRNAs had already existed in the last common ancestor of I/L/VRSs, and that the editing domain of I/L/VRSs had primarily evolved to prevent infiltration of Nva into modern proteins.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Biologija

POVEZANOST RADA