5KNN

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

5KNN の概要

• エントリーDOI: 10.2210/pdb5knn/pdb
• 分子名称: Alanine--tRNA ligase, cytoplasmic, '5'-O-(N-(L-ALANYL)-SULFAMOYL)ADENOSINE (2 entities in total)
• 機能のキーワード: trna synthetase, ligase
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cytoplasm : P49588
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 408325.18

構造登録者

Sun, L.,He, W.,Yang, X.-L. (登録日: 2016-06-28, 公開日: 2016-09-28, 最終更新日: 2023-09-27)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.68 Å)