A Structural Basis for Restricted Codon Recognition Mediated by 2-thiocytidine in tRNA Containing a Wobble Position Inosine
| Autor: | Sweta Vangaveti, Hasan DeMirci, Jessica L. Spears, Frank V. Murphy, William A. Cantara, Paul F. Agris, Kathryn L. Sarachan, Sri V. Ranganathan |
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| Rok vydání: | 2020 |
| Předmět: |
Saccharomyces cerevisiae Proteins
Speed wobble Base pair Cytidine Saccharomyces cerevisiae Wobble base pair Crystallography X-Ray Ribosome Article 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine RNA Transfer Structural Biology medicine Nucleic acid structure Codon Inosine Molecular Biology 030304 developmental biology Genetics 0303 health sciences Chemistry Computational Biology Nucleosides Transfer RNA RNA Thermodynamics 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | J Mol Biol |
| ISSN: | 0022-2836 |
| Popis: | Three of six arginine codons (CGU, CGC and CGA) are decoded by two Escherichia coli tRNA(Arg) isoacceptors. The anticodon stem and loop (ASL) domains of tRNA(Arg1) and tRNA(Arg2) both contain inosine and 2-methyladenosine modifications at positions 34 (I(34)) and 37 (m(2)A(37)). tRNA(Arg1) is also modified from cytidine to 2-thiocytidine at position 32 (s(2)C(32)). The s(2)C(32) modification is known to negate wobble codon recognition of the rare CGA codon by an unknown mechanism, while still allowing decoding of CGU and CGC. Substitution of s(2)C(32) for C(32) in the Saccharomyces cerevisiae tRNA(Ile)(IAU) anticodon stem and loop domain (ASL) negates wobble decoding of its synonymous A-ending codon, suggesting that this function of s(2)C at position 32 is a generalizable property. X-ray crystal structures of variously modified ASL(Arg1)(ICG) and ASL(Arg2)(ICG) constructs bound to cognate and wobble codons on the ribosome revealed the disruption of a C(32-)A(38) cross-loop interaction, but failed to fully explain the means by which s(2)C(32) restricts I(34) wobbling. Computational studies revealed that the adoption of a spatially broad inosine-adenosine base pair at the wobble position of the codon cannot be maintained simultaneously with the canonical ASL U-turn motif. C(32-)A(38) cross-loop interactions are required for stability of the anticodon/codon interaction in the ribosomal A-site. |
| Databáze: | OpenAIRE |
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