7UTG
2D9 nanobody to BCL11A-exZF23 fragment
Summary for 7UTG
| Entry DOI | 10.2210/pdb7utg/pdb |
| Descriptor | 2D9-V102G nanobody, SULFATE ION (3 entities in total) |
| Functional Keywords | binding protein to bcl11a-exzf23 fragment, peptide binding protein |
| Biological source | Vicugna pacos |
| Total number of polymer chains | 1 |
| Total formula weight | 14251.56 |
| Authors | Dassama, L.M.K.,Zhai, L. (deposition date: 2022-04-26, release date: 2022-12-21, Last modification date: 2024-10-23) |
| Primary citation | Shen, F.,Zheng, G.,Setegne, M.,Tenglin, K.,Izadi, M.,Xie, H.,Zhai, L.,Orkin, S.H.,Dassama, L.M.K. A Cell-Permeant Nanobody-Based Degrader That Induces Fetal Hemoglobin. Acs Cent.Sci., 8:1695-1703, 2022 Cited by PubMed Abstract: Proximity-based strategies to degrade proteins have enormous therapeutic potential in medicine, but the technologies are limited to proteins for which small molecule ligands exist. The identification of such ligands for therapeutically relevant but "undruggable" proteins remains challenging. Herein, we employed yeast surface display of synthetic nanobodies to identify a protein ligand selective for BCL11A, a critical repressor of fetal globin gene transcription. Fusion of the nanobody to a cell-permeant miniature protein and an E3 adaptor creates a degrader that depletes cellular BCL11A in differentiated primary erythroid precursor cells, thereby inducing the expression of fetal hemoglobin, a modifier of clinical severity of sickle cell disease and β-thalassemia. Our strategy provides a means of fetal hemoglobin induction through reversible, temporal modulation of BCL11A. Additionally, it establishes a new paradigm for the targeted degradation of previously intractable proteins. PubMed: 36589886DOI: 10.1021/acscentsci.2c00998 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.25 Å) |
Structure validation
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