Site-Specifically Studying Lysine Acetylation of Aminoacyl-tRNA Synthetases

by Chen, Hao; Venkat, Sumana; Hudson, Denver; Wang, Tony; Gan, Qinglei; Fan, Chenguang

Aminoacyl-tRNA synthetases (AARSs) charge their cognate tRNAs with corresponding amino acids, playing key roles in ribosomal protein synthesis. A series of proteomic studies have demonstrated that AARSs have levels of lysine acetylation much higher than those of other proteins in Escherichia coli. To study AARS acetylation, 25 site-specifically acetylated variants of four AARSs were generated by the genetic code expansion strategy. Kinetic analyses were performed to biochemically characterize the impact of site specific acetylation on AARS functions, including amino acid activation, tRNA aminoacylation, and editing activities. The results showed that impacts of acetylation were different between class I and class II AARSs and also varied among the same class of AARSs. The results also showed that acetylation of threonyl-tRNA synthetase (ThrRS) could affect its editing function. Both in vivo and in vitro studies were further performed to explore the acetylation and deacetylation processes of ThrRS. Although nonenzymatic acetylation and CobB-dependent deacetylation were concluded, the results also indicated the existence of additional modifying enzymes or mechanisms for ThrRS acetylation and deacetylation.

Journal
ACS Chemical Biology
Volume
14
Issue
2
Year
2019
Start Page
288-295
URL
https://dx.doi.org/10.1021/acschembio.8b01013
ISBN/ISSN
1554-8937; 1554-8929
DOI
10.1021/acschembio.8b01013