8SLR
Crystal Structure of mouse TRAIL
Summary for 8SLR
| Entry DOI | 10.2210/pdb8slr/pdb |
| Descriptor | Tumor necrosis factor ligand superfamily member 10, ZINC ION, CHLORIDE ION, ... (6 entities in total) |
| Functional Keywords | trail, apoptosis, pro-apoptotic, tnf superfamily, cytokine |
| Biological source | Mus musculus (house mouse) |
| Total number of polymer chains | 1 |
| Total formula weight | 20563.92 |
| Authors | |
| Primary citation | Luo, Y.,Hao, H.,Wang, Z.,Ong, C.Y.,Dutcher, R.,Xu, Y.,Liu, J.,Pedersen, L.C.,Xu, D. Heparan sulfate promotes TRAIL-induced tumor cell apoptosis. Elife, 12:-, 2024 Cited by PubMed Abstract: TRAIL (TNF-related apoptosis-inducing ligand) is a potent inducer of tumor cell apoptosis through TRAIL receptors. While it has been previously pursued as a potential anti-tumor therapy, the enthusiasm subsided due to unsuccessful clinical trials and the fact that many tumors are resistant to TRAIL. In this report, we identified heparan sulfate (HS) as an important regulator of TRAIL-induced apoptosis. TRAIL binds HS with high affinity ( = 73 nM) and HS induces TRAIL to form higher-order oligomers. The HS-binding site of TRAIL is located at the N-terminus of soluble TRAIL, which includes three basic residues. Binding to cell surface HS plays an essential role in promoting the apoptotic activity of TRAIL in both breast cancer and myeloma cells, and this promoting effect can be blocked by heparin, which is commonly administered to cancer patients. We also quantified HS content in several lines of myeloma cells and found that the cell line showing the most resistance to TRAIL has the least expression of HS, which suggests that HS expression in tumor cells could play a role in regulating sensitivity towards TRAIL. We also discovered that death receptor 5 (DR5), TRAIL, and HS can form a ternary complex and that cell surface HS plays an active role in promoting TRAIL-induced cellular internalization of DR5. Combined, our study suggests that TRAIL-HS interactions could play multiple roles in regulating the apoptotic potency of TRAIL and might be an important point of consideration when designing future TRAIL-based anti-tumor therapy. PubMed: 38265424DOI: 10.7554/eLife.90192 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.4 Å) |
Structure validation
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