6BWV
Crystal Structure of the 4-1BB/4-1BBL Complex
Summary for 6BWV
| Entry DOI | 10.2210/pdb6bwv/pdb |
| Descriptor | Tumor necrosis factor ligand superfamily member 9, Tumor necrosis factor receptor superfamily member 9, DI(HYDROXYETHYL)ETHER, ... (4 entities in total) |
| Functional Keywords | tnf superfamily, tnfr superfamily, cd137, immune system |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 4 |
| Total formula weight | 63219.64 |
| Authors | Oganesyan, V.,Gilbreth, R.N.,Baca, M. (deposition date: 2017-12-15, release date: 2018-05-09, Last modification date: 2024-10-30) |
| Primary citation | Gilbreth, R.N.,Oganesyan, V.Y.,Amdouni, H.,Novarra, S.,Grinberg, L.,Barnes, A.,Baca, M. Crystal structure of the human 4-1BB/4-1BBL complex. J. Biol. Chem., 293:9880-9891, 2018 Cited by PubMed Abstract: 4-1BBL is a member of the tumor necrosis factor (TNF) superfamily and is the ligand for the TNFR superfamily receptor, 4-1BB. 4-1BB plays an immunomodulatory role in T cells and NK cells, and agonists of this receptor have garnered strong attention as potential immunotherapy agents. Broadly speaking, the structural features of TNF superfamily members, their receptors, and ligand-receptor complexes are similar. However, a published crystal structure of human 4-1BBL suggests that it may be unique in this regard, exhibiting a three-bladed propeller-like trimer assembly that is distinctly different from that observed in other family members. This unusual structure also suggests that the human 4-1BB/4-1BBL complex may be structurally unique within the TNF/TNFR superfamily, but to date no structural data have been reported. Here we report the crystal structure of the human 4-1BB/4-1BBL complex at 2.4-Å resolution. In this structure, 4-1BBL does not adopt the unusual trimer assembly previously reported, but instead forms a canonical bell-shaped trimer typical of other TNF superfamily members. The structure of 4-1BB is also largely canonical as is the 4-1BB/4-1BBL complex. Mutational data support the 4-1BBL structure reported here as being biologically relevant, suggesting that the previously reported structure is not. Together, the data presented here offer insight into structure/function relationships in the 4-1BB/4-1BBL system and improve our structural understanding of the TNF/TNFR superfamily more broadly. PubMed: 29720399DOI: 10.1074/jbc.RA118.002803 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.4 Å) |
Structure validation
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