Structural conservation of an ancient tRNA sensor in eukaryotic glutaminyl-tRNA synthetase
- State Univ. of New York (SUNY), Buffalo, NY (United States)
- Univ. of Rochester, NY (United States). Center for Pediatric Biomedical Research
- Univ. of California, Santa Barbara, CA (United States). Dept. of Chemistry and Biochemistry
- Univ. of Rochester, NY (United States). Center for Pediatric Biomedical Research; Univ. of Rochester, NY (United States). Medical School, Dept. of Biochemistry and Biophysics
- Univ. of Rochester, NY (United States). Center for Pediatric Biomedical Research; Univ. of Rochester, NY (United States). Medical School
In all organisms, aminoacyl tRNA synthetases covalently attach amino acids to their cognate tRNAs. Many eukaryotic tRNA synthetases have acquired appended domains, whose origin, structure and function are poorly understood. The N-terminal appended domain (NTD) of glutaminyl-tRNA synthetase (GlnRS) is intriguing since GlnRS is primarily a eukaryotic enzyme, whereas in other kingdoms Gln-tRNAGln is primarily synthesized by first forming Glu-tRNAGln, followed by conversion to Gln-tRNAGln by a tRNA-dependent amidotransferase. We report a functional and structural analysis of the NTD of Saccharomyces cerevisiae GlnRS, Gln4. Yeast mutants lacking the NTD exhibit growth defects, and Gln4 lacking the NTD has reduced complementarity for tRNAGln and glutamine. The 187-amino acid Gln4 NTD, crystallized and solved at 2.3 Å resolution, consists of two subdomains, each exhibiting an extraordinary structural resemblance to adjacent tRNA specificity determining domains in the GatB subunit of the GatCAB amidotransferase, which forms Gln-tRNAGln. These subdomains are connected by an apparent hinge comprised of conserved residues. Mutation of these amino acids produces Gln4 variants with reduced affinity for tRNAGln, consistent with a hinge-closing mechanism proposed for GatB recognition of tRNA. Our results suggest a possible origin and function of the NTD that would link the phylogenetically diverse mechanisms of Gln-tRNAGln synthesis.
- Research Organization:
- SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States). Stanford Synchrotron Radiation Lightsource (SSRL)
- Sponsoring Organization:
- USDOE Office of Science (SC), Biological and Environmental Research (BER); Defense Threat Reduction Agency (DTRA); National Institutes of Health (NIH)
- Grant/Contract Number:
- AC02-76SF00515; HDTRA1-10- C-0057; U54 GM074899; GM63713
- OSTI ID:
- 1625487
- Journal Information:
- Nucleic Acids Research, Vol. 40, Issue 8; ISSN 0305-1048
- Publisher:
- Oxford University PressCopyright Statement
- Country of Publication:
- United States
- Language:
- English
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