21AA
Structure of Human Aspartate--tRNA ligase 3-154 with linker and FC : ATYR0101
This is a non-PDB format compatible entry.
Summary for 21AA
| Entry DOI | 10.2210/pdb21aa/pdb |
| EMDB information | 67441 |
| Descriptor | Aspartate--tRNA ligase, cytoplasmic,linker+FC (1 entity in total) |
| Functional Keywords | apoptosis, fibrosis, t-rna synthase, myofibroblast |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 2 |
| Total formula weight | 91055.35 |
| Authors | |
| Primary citation | Adams, R.A.,Wang, Y.T.,Barber, A.G.,Hamel, K.,Imfeld, A.,Burman, L.,Rauch, K.,Chong, Y.E.,Villanueva, A.,Guy, L.,Liu, W.,Manzo, C.,Klopp-Savino, S.,Polizzi, C.,Stamps, J.,Pastenes, M.,Tian, H.,Fung, C.P.,Zhang, Y.,Hugo Ho, K.W.,Sangiorgi, B.,Dillingham, B.,Brust, T.F.,Chiang, K.P.,Wu, Z.,Xu, Z.,Burkart, C.,Nangle, L.A. Natural Asp-tRNA Synthetase Fragment Targets Myofibroblasts to Abrogate Tissue Fibrosis. J.Biol.Chem., :113586-113586, 2026 Cited by PubMed Abstract: Fibrosis remains a major global health challenge with limited therapies that only slow disease progression. While the aminoacyl-tRNA synthetase (aaRS) family is known to utilize evolutionarily appended domains as extracellular signaling molecules, their role in regulating the homeostasis of the fibrotic process is poorly defined. We identify a natural proteolytic fragment of aspartyl-tRNA synthetase (DARS), termed DARS-N1, that selectively triggers apoptosis in myofibroblasts by targeting latent-transforming growth factor beta binding protein 1 (LTBP-1) on the extracellular matrix (ECM). This active N-terminal fragment of DARS reduces focal adhesion kinase (FAK) activation in undifferentiated fibroblasts and myofibroblasts, while only myofibroblasts exhibit inadequate cell-matrix attachment leading to loss of anchorage-dependent survival and promotion of apoptosis. We utilized ATYR0101, a therapeutic form of DARS-N1 engineered for extended serum exposure, to demonstrate anti-fibrotic activity in lung (bleomycin). Spatial transcriptomics analysis showed that ATYR0101 activates a restorative program promoting the return to a healthy state. These findings highlight ATYR0101's potential as a transformative therapy for disrupting the process of chronic tissue fibrosis. PubMed: 42815638DOI: 10.1016/j.jbc.2026.113586 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (4.96 Å) |
Structure validation
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