7NEL

ER-PRS*(+) (Y537S) in complex with estradiol and SRC-2 coactivator peptide

7NEL の概要

• エントリーDOI: 10.2210/pdb7nel/pdb
• 関連するPDBエントリー: 7NDO
• 分子名称: Estrogen receptor, Nuclear receptor coactivator 2, ESTRADIOL, ... (8 entities in total)
• 機能のキーワード: human estrogen receptor alpha, hera-lbd, estradiol, src-2, ligand binding domain, er, transcription
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 62079.18

構造登録者

Kriegel, M.,Muller, Y.A. (登録日: 2021-02-04, 公開日: 2021-08-25, 最終更新日: 2024-10-23)

主引用文献

Kriegel, M.,Wiederanders, H.J.,Alkhashrom, S.,Eichler, J.,Muller, Y.A.
A PROSS-designed extensively mutated estrogen receptor alpha variant displays enhanced thermal stability while retaining native allosteric regulation and structure.
Sci Rep, 11:10509-10509, 2021

PubMed Abstract: Protein stability limitations often hamper the exploration of proteins as drug targets. Here, we show that the application of PROSS server algorithms to the ligand-binding domain of human estrogen receptor alpha (hERα) enabled the development of variant ER that comprises 24 amino acid substitutions and exhibits multiple improved characteristics. The protein displays enhanced production rates in E. coli, crystallizes readily and its thermal stability is increased significantly by 23 °C. hERα is a nuclear receptor (NR) family member. In NRs, protein function is allosterically regulated by its interplay with small molecule effectors and the interaction with coregulatory proteins. The in-depth characterization of ER shows that these cooperative effects are fully preserved despite that 10% of all residues were substituted Crystal structures reveal several salient features, i.e. the introduction of a tyrosine corner in a helix-loop-helix segment and the formation of a novel surface salt bridge network possibly explaining the enhanced thermal stability. ER shows that prior successes in computational approaches for stabilizing proteins can be extended to proteins with complex allosteric regulatory behaviors as present in NRs. Since NRs including hERα are implicated in multiple diseases, our ER variant shows significant promise for facilitating the development of novel hERα modulators.

PubMed: 34006920
DOI: 10.1038/s41598-021-89785-1

実験手法

X-RAY DIFFRACTION (1.45 Å)