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Updated: Jul 8, 2026
08:04
DNA Sequence Recognition by DNA Primase Using High-Throughput Primase Profiling
Published on: October 8, 2019
Distinct domains of tRNA synthetase recognize the same base pair
Kirk Beebe1, Marissa Mock, Eve Merriman
1Department of Molecular Biology and Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Nature
|January 4, 2008
Summary
Cells prevent protein synthesis errors using aminoacyl-tRNA synthetases. This study reveals a novel editing mechanism in alanyl-tRNA synthetase that independently recognizes mischarged tRNAs, safeguarding against mistranslation.
Area of Science:
- Molecular Biology
- Biochemistry
- Genetics
Background:
- Protein synthesis accuracy is crucial, with errors (mistranslation) leading to pathologies like neurodegeneration.
- Aminoacyl-tRNA synthetases (aaRS) ensure fidelity through aminoacylation and editing.
- Mistaking glycine or serine for alanine is a common source of mistranslation.
Purpose of the Study:
- To investigate the structural determinants of tRNA recognition by alanyl-tRNA synthetase (AlaRS) during editing.
- To determine if the editing site uses the same recognition mechanism as the aminoacylation site.
- To explore the evolutionary conservation of editing-related structural motifs.
Main Methods:
- Utilized an artificial recombinant fragment of AlaRS to study its editing site.
- Investigated the recognition of mischarged tRNA(Ala) by the editing domain.
- Analyzed evolutionary distribution of identified structural motifs in genome-encoded protein fragments.
Main Results:
- The editing site of AlaRS employs a distinct structural motif for tRNA(Ala) recognition, separate from the aminoacylation site.
- This editing motif is conserved in naturally occurring protein fragments across evolution.
- These conserved motifs also recognize mischarged tRNA(Ala), indicating multiple evolutionary safeguards.
Conclusions:
- AlaRS possesses independent structural motifs for aminoacylation and editing, ensuring high fidelity.
- Evolution has conserved specific protein fragments with editing capabilities to prevent mistranslation.
- Multiple distinct recognition mechanisms ensure cellular protection against mistaking glycine/serine for alanine during protein synthesis.
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