Naslov
Reassessment of LeuRS discriminatory power unveils norvaline as a prime quality control target

Autori
Cvetešić, Nevena ; Palencia, Andres ; Cusack, Stephen ; Gruić-Sovulj, Ita

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

Izvornik
Biomolecular complexes and assemblies / Hozić, Amela ; Vuletić, Tomislav - Zagreb, 2014, 60-60

ISBN
978-953-7941-02-4

Skup
12th Greta Pifat Mrzljak International School of Biohphysics

Mjesto i datum
Primošten, Hrvatska, 27.09.2014. - 06.10.2014

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Nije recenziran

Ključne riječi
leucyl-tRNA synthetase; proofreading; isoleucine; norvaline

Sažetak
Leucyl-tRNA synthetases (LeuRS) covalently couple tRNALeu with leucine, and thereby provide the pool of Leu-tRNALeu for ribosomal protein synthesis. LeuRS may also activate and transfer to tRNALeu structurally and chemically similar norvaline, a non–canonical amino acid that accumulates in Escherichia coli under micro-aerobic conditions. However, incorporation of norvaline into proteins is prevented by efficient intrinsic LeuRS hydrolytic activity toward norvalyl-tRNALeu within a dedicated post-transfer editing domain. In spite of the prevailing opinion that noncognate isoleucine mimics leucine well in the LeuRS synthetic reactions and thus requires editing to prevent errors in leucyl-tRNALeu synthesis, we now demonstrate that isoleucine is discriminated with high specificity within the synthetic site. Thermodynamic, structural and kinetic approaches establish that both very weak ground state binding and the decreased rate of the chemical step contribute to isoleucine discrimination. These results were complemented by in vivo experiments, where we show that while E. coli strain with editing deficient LeuRS grows normally in the presence of high isoleucine concentration, it displays growth defects under micro-aerobic conditions where norvaline accumulates. Our results reveal that LeuRS-mediated translational quality control represents the essential part of the major E. coli adaptive response necessary for survival in environments with low oxygen levels.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Biologija

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