5E6C

Glucocorticoid receptor DNA binding domain - CCL2 NF-kB response element complex

5E6C の概要

• エントリーDOI: 10.2210/pdb5e6c/pdb
• 関連するPDBエントリー: 5E69 5E6A 5E6B 5E6D
• 分子名称: Glucocorticoid receptor, DNA (5'-D(*AP*GP*TP*GP*GP*AP*AP*AP*TP*TP*CP*CP*CP*AP*CP*T)-3'), DNA (5'-D(*AP*GP*TP*GP*GP*GP*AP*AP*TP*TP*TP*CP*CP*AP*CP*T)-3'), ... (5 entities in total)
• 機能のキーワード: dna binding protein, dna binding protein-dna complex, dna binding protein/dna
• 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: 35576.64

構造登録者

Hudson, W.H.,Rye, E.A.,Herbst, A.G.,Ortlund, E.A. (登録日: 2015-10-09, 公開日: 2017-02-08, 最終更新日: 2024-03-06)

主引用文献

Hudson, W.H.,Vera, I.M.S.,Nwachukwu, J.C.,Weikum, E.R.,Herbst, A.G.,Yang, Q.,Bain, D.L.,Nettles, K.W.,Kojetin, D.J.,Ortlund, E.A.
Cryptic glucocorticoid receptor-binding sites pervade genomic NF-kappa B response elements.
Nat Commun, 9:1337-1337, 2018

PubMed Abstract: Glucocorticoids (GCs) are potent repressors of NF-κB activity, making them a preferred choice for treatment of inflammation-driven conditions. Despite the widespread use of GCs in the clinic, current models are inadequate to explain the role of the glucocorticoid receptor (GR) within this critical signaling pathway. GR binding directly to NF-κB itself-tethering in a DNA binding-independent manner-represents the standing model of how GCs inhibit NF-κB-driven transcription. We demonstrate that direct binding of GR to genomic NF-κB response elements (κBREs) mediates GR-driven repression of inflammatory gene expression. We report five crystal structures and solution NMR data of GR DBD-κBRE complexes, which reveal that GR recognizes a cryptic response element between the binding footprints of NF-κB subunits within κBREs. These cryptic sequences exhibit high sequence and functional conservation, suggesting that GR binding to κBREs is an evolutionarily conserved mechanism of controlling the inflammatory response.

PubMed: 29626214
DOI: 10.1038/s41467-018-03780-1

実験手法

X-RAY DIFFRACTION (2.2 Å)