9CU8
Crystal Structure of TNFR2 TNFR2_mb1 Complex
Summary for 9CU8
| Entry DOI | 10.2210/pdb9cu8/pdb |
| Descriptor | TNFR2_mb1, Tumor necrosis factor receptor superfamily member 1B (3 entities in total) |
| Functional Keywords | de novo protein, tnfr2, antagonists and agonists, tnfr1 |
| Biological source | synthetic construct More |
| Total number of polymer chains | 2 |
| Total formula weight | 32079.61 |
| Authors | Bera, A.K.,Glogl, M.,Baker, D. (deposition date: 2024-07-26, release date: 2024-12-04, Last modification date: 2024-12-18) |
| Primary citation | Glogl, M.,Krishnakumar, A.,Ragotte, R.J.,Goreshnik, I.,Coventry, B.,Bera, A.K.,Kang, A.,Joyce, E.,Ahn, G.,Huang, B.,Yang, W.,Chen, W.,Sanchez, M.G.,Koepnick, B.,Baker, D. Target-conditioned diffusion generates potent TNFR superfamily antagonists and agonists. Science, 386:1154-1161, 2024 Cited by PubMed Abstract: Despite progress in designing protein-binding proteins, the shape matching of designs to targets is lower than in many native protein complexes, and design efforts have failed for the tumor necrosis factor receptor 1 (TNFR1) and other protein targets with relatively flat and polar surfaces. We hypothesized that free diffusion from random noise could generate shape-matched binders for challenging targets and tested this approach on TNFR1. We obtain designs with low picomolar affinity whose specificity can be completely switched to other family members using partial diffusion. Designs function as antagonists or as superagonists when presented at higher valency for OX40 and 4-1BB. The ability to design high-affinity and high-specificity antagonists and agonists for pharmacologically important targets in silico presages a coming era in protein design in which binders are made by computation rather than immunization or random screening approaches. PubMed: 39636970DOI: 10.1126/science.adp1779 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.96 Å) |
Structure validation
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