5KNN

Evolutionary gain of alanine mischarging to non-cognate tRNAs with a G4:U69 base pair

Summary for 5KNN

• Entry DOI: 10.2210/pdb5knn/pdb
• Descriptor: Alanine--tRNA ligase, cytoplasmic, '5'-O-(N-(L-ALANYL)-SULFAMOYL)ADENOSINE (2 entities in total)
• Functional Keywords: trna synthetase, ligase
• Biological source: Homo sapiens (Human)
• Cellular location: Cytoplasm : P49588
• Total number of polymer chains: 8
• Total formula weight: 408325.18

Authors

Sun, L.,He, W.,Yang, X.-L. (deposition date: 2016-06-28, release date: 2016-09-28, Last modification date: 2023-09-27)

Primary citation

Sun, L.,Gomes, A.C.,He, W.,Zhou, H.,Wang, X.,Pan, D.W.,Schimmel, P.,Pan, T.,Yang, X.L.
Evolutionary Gain of Alanine Mischarging to Noncognate tRNAs with a G4:U69 Base Pair.
J.Am.Chem.Soc., 138:12948-12955, 2016

PubMed Abstract: Fidelity of translation, which is predominately dictated by the accuracy of aminoacyl-tRNA synthetases in pairing amino acids with correct tRNAs, is of central importance in biology. Yet, deliberate modifications of translational fidelity can be beneficial. Here we found human and not E. coli AlaRS has an intrinsic capacity for mispairing alanine onto nonalanyl-tRNAs including tRNA. Consistently, a cysteine-to-alanine substitution was found in a reporter protein expressed in human cells. All human AlaRS-mischarged tRNAs have a G4:U69 base pair in the acceptor stem. The base pair is required for the mischarging. By solving the crystal structure of human AlaRS and comparing it to that of E. coli AlaRS, we identified a key sequence divergence between eukaryotes and bacteria that influences mischarging. Thus, the expanded tRNA specificity of AlaRS appears to be an evolutionary gain-of-function to provide posttranscriptional alanine substitutions in eukaryotic proteins for potential regulations.

PubMed: 27622773
DOI: 10.1021/jacs.6b07121

Experimental method

X-RAY DIFFRACTION (2.68 Å)