Aminoacyl-tRNA synthetases (aaRSs) are a group of essential translation enzymes, each of which catalyzes the ligation of a specific amino acid to its cognate tRNA (aa + tRNA — aa-tRNA). The resultant aa-tRNAs are then delivered to ribosomes to decipher mRNA codons through base pairing with the anticodon of the aa-tRNA. Arc1p is an aaRS cofactor that binds tRNA and forms a ternary complex with glutamyl-tRNA synthetase (GluRSc) and methionyl-tRNA synthetase (MetRS) in the yeast cytoplasm to regulate their catalytic activities and subcellular distributions. Upon dissociation from Arc1p, GluRSc and MetRS are respectively targeted to mitochondria and the nucleus to coordinate OXPHOS (oxidative phosphorylation) gene expression. Despite the fact that Arc1p is not involved in any known carboxylation/decarboxylation reaction and lacks the canonical sequence “AMKM” of biotin-binding domains, it is a natural target of biotin modification. Arc1p is so far the only known yeast protein that is not involved in CO2 transfer, but is biotinylated. Biotinylation of Arc1p is highly specific and occurs only at K86 within the SSKD motif of its N domain. This covalent modification is catalyzed by the one and only biotin protein ligase Bpl1p in yeast. However, the biological significance of this post-translational modification remains elusive. The proposal presented herein elaborates a three-year project, in which we aim to study the effect of biotinylation on Arc1p5s structure and function in particular and the biological significance of this type of post-translational modification in general. Specific aims include (1) elucidating the effect of biotinylation on Arc1p5s structural and function, and (2) delineating the mechanism of Arc1p biotinylation by Bpl1p.
|Effective start/end date
|1/08/17 → 31/07/18
UN Sustainable Development Goals
In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This project contributes towards the following SDG(s):
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