7UTG

2D9 nanobody to BCL11A-exZF23 fragment

7UTG の概要

• エントリーDOI: 10.2210/pdb7utg/pdb
• 分子名称: 2D9-V102G nanobody, SULFATE ION (3 entities in total)
• 機能のキーワード: binding protein to bcl11a-exzf23 fragment, peptide binding protein
• 由来する生物種: Vicugna pacos
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 14251.56

構造登録者

Dassama, L.M.K.,Zhai, L. (登録日: 2022-04-26, 公開日: 2022-12-21, 最終更新日: 2024-10-23)

主引用文献

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

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: 36589886
DOI: 10.1021/acscentsci.2c00998

実験手法

X-RAY DIFFRACTION (1.25 Å)