ArticleRNA biology2018
An alternative conformation of human TrpRS suggests a role of zinc in activating non-enzymatic function.
Article in RNA biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
11 citing papers in PubMed, 16 citations in OpenAlex.
- Zinc-Releasing Fibrous Scaffolds Modulate Fibroblast, Endothelial, and Macrophage Interactions for Vascularized Tissue Engineering.ACS applied materials & interfaces · 2026Article
- Prognostic Value of Tryptophanyl-tRNA Synthetase in Sepsis Combined with Kidney Dysfunction or Urinary Tract Infection: A Prospective Observational Study.Diagnostics (Basel, Switzerland) · 2025Article
- The crystal structures of apo and tryptophan-bound tryptophanyl-tRNA synthetase from Neisseria gonorrhoeae.Acta crystallographica. Section F, Structural biology communications · 2025Article
- The high-affinity tryptophan uptake transport system in human cells.Biochemical Society transactions · 2024Review
- Peculiarities of aminoacyl-tRNA synthetases from trypanosomatids.The Journal of biological chemistry · 2021Article
- The zinc-binding domain of mammalian prolyl-tRNA synthetase is indispensable for catalytic activity and organism viability.iScience · 2021Article
- Tryptophanyl-tRNA Synthetase, a Novel Damage-Induced Cytokine, Significantly Increases the Therapeutic Effects of Endometrial Stem Cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
- Design and synthesis of novel spirooxindole-indenoquinoxaline derivatives as novel tryptophanyl-tRNA synthetase inhibitors.Molecular diversity · 2020Article
- Matrix metalloproteinases inactivate the proinflammatory functions of secreted moonlighting tryptophanyl-tRNA synthetase.The Journal of biological chemistry · 2019Article
- Unique roles of tryptophanyl-tRNA synthetase in immune control and its therapeutic implications.Experimental & molecular medicine · 2019Review
- Transfer RNA function and evolution.RNA biology · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
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.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.