5UJJ

Crystal structure of human H130R tryptophanyl-tRNA synthetase in complex with TrpAMP

5UJJ の概要

• エントリーDOI: 10.2210/pdb5ujj/pdb
• 関連するPDBエントリー: 5UJI
• 分子名称: Tryptophan--tRNA ligase, cytoplasmic, TRYPTOPHANYL-5'AMP, MAGNESIUM ION, ... (4 entities in total)
• 機能のキーワード: rossmann-fold catalytic domain, anti-codon binding domain, h130r mutation, ligase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 110693.78

構造登録者

Xu, X.,Yang, X.-L. (登録日: 2017-01-18, 公開日: 2018-01-17, 最終更新日: 2023-10-04)

主引用文献

Xu, X.,Zhou, H.,Zhou, Q.,Hong, F.,Vo, M.N.,Niu, W.,Wang, Z.,Xiong, X.,Nakamura, K.,Wakasugi, K.,Schimmel, P.,Yang, X.L.
An alternative conformation of human TrpRS suggests a role of zinc in activating non-enzymatic function.
RNA Biol, 15:649-658, 2018

PubMed Abstract: Tryptophanyl-tRNA synthetase (TrpRS) in vertebrates contains a N-terminal extension in front of the catalytic core. Proteolytic removal of the N-terminal 93 amino acids gives rise to T2-TrpRS, which has potent anti-angiogenic activity mediated through its extracellular interaction with VE-cadherin. Zinc has been shown to have anti-angiogenic effects and can bind to human TrpRS. However, the connection between zinc and the anti-angiogenic function of TrpRS has not been explored. Here we report that zinc binding can induce structural relaxation in human TrpRS to facilitate the proteolytic generation of a T2-TrpRS-like fragment. The zinc-binding site is likely to be contained within T2-TrpRS, and the zinc-bound conformation of T2-TrpRS is mimicked by mutation H130R. We determined the crystal structure of H130R T2-TrpRS at 2.8 Å resolution, which reveals drastically different conformation from that of wild-type (WT) T2-TrpRS. The conformational change creates larger binding surfaces for VE-cadherin as suggested by molecular dynamic simulations. Surface plasmon resonance analysis indicates more than 50-fold increase in binding affinity of H130R T2-TrpRS for VE-cadherin, compared to WT T2-TrpRS. The enhanced interaction is also confirmed by a cell-based binding analysis. These results suggest that zinc plays an important role in activating TrpRS for angiogenesis regulation.

PubMed: 28910573
DOI: 10.1080/15476286.2017.1377868

実験手法

X-RAY DIFFRACTION (2.1 Å)