5UJI
Crystal structure of human T2-Tryptophanyl-tRNA synthetase with H130R mutation
Summary for 5UJI
| Entry DOI | 10.2210/pdb5uji/pdb |
| Related | 5UJJ |
| Descriptor | Tryptophan--tRNA ligase, cytoplasmic (1 entity in total) |
| Functional Keywords | rossmann-fold catalytic domain, anti-codon binding domain, h130r mutation, ligase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 2 |
| Total formula weight | 89289.81 |
| Authors | Xu, X.,Yang, X.-L. (deposition date: 2017-01-18, release date: 2018-01-17, Last modification date: 2023-10-04) |
| Primary citation | 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 Cited by 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: 28910573DOI: 10.1080/15476286.2017.1377868 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.79 Å) |
Structure validation
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