8P6Q
Racemic structure of TNFR1 cysteine-rich domain
Summary for 8P6Q
| Entry DOI | 10.2210/pdb8p6q/pdb |
| Descriptor | Tumor necrosis factor-binding protein 1, D-TNFR-1 CRD2, SULFATE ION, ... (4 entities in total) |
| Functional Keywords | racemic, chemical synthesis, cysteine-rich, cytokine receptor, receptor mimic, cytokine |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 2 |
| Total formula weight | 11559.65 |
| Authors | Lander, A.J.,Jin, Y.,Luk, L.Y.P. (deposition date: 2023-05-28, release date: 2024-01-24, Last modification date: 2024-10-23) |
| Primary citation | Lander, A.J.,Kong, Y.,Jin, Y.,Wu, C.,Luk, L.Y.P. Deciphering the Synthetic and Refolding Strategy of a Cysteine-Rich Domain in the Tumor Necrosis Factor Receptor (TNF-R) for Racemic Crystallography Analysis and d-Peptide Ligand Discovery. Acs Bio Med Chem Au, 4:68-76, 2024 Cited by PubMed Abstract: Many cell-surface receptors are promising targets for chemical synthesis because of their critical roles in disease development. This synthetic approach enables investigations by racemic protein crystallography and ligand discovery by mirror-image methodologies. However, due to their complex nature, the chemical synthesis of a receptor can be a significant challenge. Here, we describe the chemical synthesis and folding of a central, cysteine-rich domain of the cell-surface receptor tumor necrosis factor 1 which is integral to binding of the cytokine TNF-α, namely, TNFR-1 CRD2. Racemic protein crystallography at 1.4 Å confirmed that the native binding conformation was preserved, and TNFR-1 CRD2 maintained its capacity to bind to TNF-α ( ≈ 7 nM). Encouraged by this discovery, we carried out mirror-image phage display using the enantiomeric receptor mimic and identified a d-peptide ligand for TNFR-1 CRD2 ( = 1 μM). This work demonstrated that cysteine-rich domains, including the central domains, can be chemically synthesized and used as mimics for investigations. PubMed: 38404743DOI: 10.1021/acsbiomedchemau.3c00060 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.4 Å) |
Structure validation
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