3UH0

Crystal structure of the yeast mitochondrial threonyl-tRNA synthetase (MST1) in complex with threonyl sulfamoyl adenylate

Summary for 3UH0

• Entry DOI: 10.2210/pdb3uh0/pdb
• Related: 3UGQ 3UGT
• Descriptor: Threonyl-tRNA synthetase, mitochondrial, ZINC ION, 5'-O-(N-(L-THREONYL)-SULFAMOYL)ADENOSINE, ... (5 entities in total)
• Functional Keywords: threonyl-trna synthetase, trna, threonine trna, threonyl adenylate, threonyl sulfamoyl adenylate, aminoacyl-trna synthetase class ii, ligase
• Biological source: Saccharomyces cerevisiae (Baker's yeast)
• Cellular location: Mitochondrion matrix: P07236
• Total number of polymer chains: 1
• Total formula weight: 54082.79

Authors

Peterson, K.M.,Ling, J.,Simonovic, I.,Cho, C.,Soll, D.,Simonovic, M. (deposition date: 2011-11-03, release date: 2012-02-22, Last modification date: 2024-02-28)

Primary citation

Ling, J.,Peterson, K.M.,Simonovic, I.,Cho, C.,Soll, D.,Simonovic, M.
Yeast mitochondrial threonyl-tRNA synthetase recognizes tRNA isoacceptors by distinct mechanisms and promotes CUN codon reassignment.
Proc.Natl.Acad.Sci.USA, 109:3281-3286, 2012

PubMed Abstract: Aminoacyl-tRNA synthetases (aaRSs) ensure faithful translation of mRNA into protein by coupling an amino acid to a set of tRNAs with conserved anticodon sequences. Here, we show that in mitochondria of Saccharomyces cerevisiae, a single aaRS (MST1) recognizes and aminoacylates two natural tRNAs that contain anticodon loops of different size and sequence. Besides a regular tRNA(2Thr) with a threonine (Thr) anticodon, MST1 also recognizes an unusual tRNA(1Thr), which contains an enlarged anticodon loop and an anticodon triplet that reassigns the CUN codons from leucine to threonine. Our data show that MST1 recognizes the anticodon loop in both tRNAs, but employs distinct recognition mechanisms. The size but not the sequence of the anticodon loop is critical for tRNA(1Thr) recognition, whereas the anticodon sequence is essential for aminoacylation of tRNA(2Thr). The crystal structure of MST1 reveals that, while lacking the N-terminal editing domain, the enzyme closely resembles the bacterial threonyl-tRNA synthetase (ThrRS). A detailed structural comparison with Escherichia coli ThrRS, which is unable to aminoacylate tRNA(1Thr), reveals differences in the anticodon-binding domain that probably allow recognition of the distinct anticodon loops. Finally, our mutational and modeling analyses identify the structural elements in MST1 (e.g., helix α11) that define tRNA selectivity. Thus, MTS1 exemplifies that a single aaRS can recognize completely divergent anticodon loops of natural isoacceptor tRNAs and that in doing so it facilitates the reassignment of the genetic code in yeast mitochondria.

PubMed: 22343532
DOI: 10.1073/pnas.1200109109

Experimental method

X-RAY DIFFRACTION (2 Å)