A WHEP domain regulates the dynamic structure and activity of Caenorhabditis elegans glycyl-tRNA synthetase

Chih Yao Chang, Chin I. Chien, Chia Pei Chang, Bo Chun Lin, Chien Chia Wang

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

WHEP domains exist in certain eukaryotic aminoacyl-tRNA synthetases and play roles in tRNA or protein binding. We present evidence herein that cytoplasmic and mitochondrial forms of Caenorhabditis elegans glycyl-tRNA synthetase (CeGlyRS) are encoded by the same gene (CeGRS1) through alternative initiation of translation. The cytoplasmic form possessed an N-terminal WHEP domain, whereas its mitochondrial isoform possessed an extra N-terminal sequence consisting of an mitochondrial targeting signal and an appended domain. Cross-species complementation assays showed that CeGRS1 effectively rescued the cytoplasmic and mitochondrial defects of a yeast GRS1 knock-out strain. Although both forms of CeGlyRS efficiently charged the cytoplasmic tRNAs Gly of C. elegans, the mitochondrial form was much more efficient than its cytoplasmic counterpart in charging the mitochondrial tRNA Gly isoacceptor, which carries a defective TψC hairpin. Despite the WHEP domain per se lacking tRNA binding activity, deletion of this domain reduced the catalytic efficiency of the enzyme. Most interestingly, the deletion mutant possessed a higher thermal stability and a somewhat lower structural flexibility. Our study suggests a role for the WHEP domain as a regulator of the dynamic structure and activity of the enzyme.

Original languageEnglish
Pages (from-to)16567-16575
Number of pages9
JournalJournal of Biological Chemistry
Volume291
Issue number32
DOIs
StatePublished - 5 Aug 2016

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