7A78

Crystal structure of RXR beta LBD in complexes with palmitic acid and GRIP-1 peptide

7A78 の概要

• エントリーDOI: 10.2210/pdb7a78/pdb
• 分子名称: Retinoic acid receptor RXR-beta, Nuclear receptor coactivator 2, PALMITIC ACID, ... (6 entities in total)
• 機能のキーワード: rxrb, steroid hormone receptor, inhibitor, lipid binding, fatty acid, structural genomics consortium, sgc, dna binding protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 28787.77

構造登録者

Chaikuad, A.,Merk, D.,Knapp, S.,Structural Genomics Consortium (SGC) (登録日: 2020-08-27, 公開日: 2020-10-21, 最終更新日: 2024-01-31)

主引用文献

Chaikuad, A.,Pollinger, J.,Ruhl, M.,Ni, X.,Kilu, W.,Heering, J.,Merk, D.
Comprehensive Set of Tertiary Complex Structures and Palmitic Acid Binding Provide Molecular Insights into Ligand Design for RXR Isoforms.
Int J Mol Sci, 21:-, 2020

PubMed Abstract: The retinoid X receptor (RXR) is a ligand-sensing transcription factor acting mainly as a universal heterodimer partner for other nuclear receptors. Despite presenting as a potential therapeutic target for cancer and neurodegeneration, adverse effects typically observed for RXR agonists, likely due to the lack of isoform selectivity, limit chemotherapeutic application of currently available RXR ligands. The three human RXR isoforms exhibit different expression patterns; however, they share high sequence similarity, presenting a major obstacle toward the development of subtype-selective ligands. Here, we report the discovery of the saturated fatty acid, palmitic acid, as an RXR ligand and disclose a uniform set of crystal structures of all three RXR isoforms in an active conformation induced by palmitic acid. A structural comparison revealed subtle differences among the RXR subtypes. We also observed an ability of palmitic acid as well as myristic acid and stearic acid to induce recruitment of steroid receptor co-activator 1 to the RXR ligand-binding domain with low micromolar potencies. With the high, millimolar endogenous concentrations of these highly abundant lipids, our results suggest their potential involvement in RXR signaling.

PubMed: 33187070
DOI: 10.3390/ijms21228457

実験手法

X-RAY DIFFRACTION (1.72 Å)