5THH

Crystal structure of a human tyrosyl-tRNA synthetase mutant

5THH の概要

• エントリーDOI: 10.2210/pdb5thh/pdb
• 関連するPDBエントリー: 5THL
• 分子名称: Tyrosine--tRNA ligase, cytoplasmic, TYROSINE (3 entities in total)
• 機能のキーワード: tyrosyl-trna synthetase, cmt mutant, ligase
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cytoplasm : P54577
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 38573.66

構造登録者

Blocquel, D.,Yang, X.L. (登録日: 2016-09-29, 公開日: 2017-05-17, 最終更新日: 2023-10-04)

主引用文献

Blocquel, D.,Li, S.,Wei, N.,Daub, H.,Sajish, M.,Erfurth, M.L.,Kooi, G.,Zhou, J.,Bai, G.,Schimmel, P.,Jordanova, A.,Yang, X.L.
Alternative stable conformation capable of protein misinteraction links tRNA synthetase to peripheral neuropathy.
Nucleic Acids Res., 45:8091-8104, 2017

PubMed Abstract: While having multiple aminoacyl-tRNA synthetases implicated in Charcot-Marie-Tooth (CMT) disease suggests a common mechanism, a defect in enzymatic activity is not shared among the CMT-causing mutants. Protein misfolding is a common hypothesis underlying the development of many neurological diseases. Its process usually involves an initial reduction in protein stability and then the subsequent oligomerization and aggregation. Here, we study the structural effect of three CMT-causing mutations in tyrosyl-tRNA synthetase (TyrRS or YARS). Through various approaches, we found that the mutations do not induce changes in protein secondary structures, or shared effects on oligomerization state and stability. However, all mutations provide access to a surface masked in the wild-type enzyme, and that access correlates with protein misinteraction. With recent data on another CMT-linked tRNA synthetase, we suggest that an inherent plasticity, engendering the formation of alternative stable conformations capable of aberrant interactions, links the tRNA synthetase family to CMT.

PubMed: 28531329
DOI: 10.1093/nar/gkx455

実験手法

X-RAY DIFFRACTION (1.959 Å)