4G85

Crystal structure of human HisRS

4G85 の概要

• エントリーDOI: 10.2210/pdb4g85/pdb
• 関連するPDBエントリー: 4G84
• 分子名称: Histidine-tRNA ligase, cytoplasmic (1 entity in total)
• 機能のキーワード: synthetase, ligase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: P12081
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 116858.69

構造登録者

Wei, Z.,Wu, J.,Zhou, J.J.,Yang, X.-L.,Zhang, M.,Schimmel, P. (登録日: 2012-07-21, 公開日: 2012-09-26, 最終更新日: 2023-09-13)

主引用文献

Xu, Z.,Wei, Z.,Zhou, J.J.,Ye, F.,Lo, W.S.,Wang, F.,Lau, C.F.,Wu, J.,Nangle, L.A.,Chiang, K.P.,Yang, X.L.,Zhang, M.,Schimmel, P.
Internally Deleted Human tRNA Synthetase Suggests Evolutionary Pressure for Repurposing.
Structure, 20:1470-1477, 2012

PubMed Abstract: Aminoacyl-tRNA synthetases (AARSs) catalyze aminoacylation of tRNAs in the cytoplasm. Surprisingly, AARSs also have critical extracellular and nuclear functions. Evolutionary pressure for new functions might be manifested by splice variants that skip only an internal catalytic domain (CD) and link noncatalytic N- and C-terminal polypeptides. Using disease-associated histidyl-tRNA synthetase (HisRS) as an example, we found an expressed 171-amino acid protein (HisRSΔCD) that deleted the entire CD, and joined an N-terminal WHEP to the C-terminal anticodon-binding domain (ABD). X-ray crystallography and three-dimensional NMR revealed the structures of human HisRS and HisRSΔCD. In contrast to homodimeric HisRS, HisRSΔCD is monomeric, where rupture of the ABD's packing with CD resulted in a dumbbell-like structure of flexibly linked WHEP and ABD domains. In addition, the ABD of HisRSΔCD presents a distinct local conformation. This natural internally deleted HisRS suggests evolutionary pressure to reshape AARS tertiary and quaternary structures for repurposing.

PubMed: 22958643
DOI: 10.1016/j.str.2012.08.001

実験手法

X-RAY DIFFRACTION (3.11 Å)