5E69

Glucocorticoid receptor DNA binding domain - IL8 NF-kB response element complex

Summary for 5E69

• Entry DOI: 10.2210/pdb5e69/pdb
• Related: 5E6A 5E6B 5E6C 5E6D
• Descriptor: Glucocorticoid receptor, DNA (5'-D(*GP*AP*GP*GP*AP*AP*AP*TP*TP*CP*CP*AP*CP*GP*AP*T)-3'), DNA (5'-D(*AP*TP*CP*GP*TP*GP*GP*AP*AP*TP*TP*TP*CP*CP*TP*C)-3'), ... (5 entities in total)
• Functional Keywords: dna binding proteins, dna binding protein-dna complex, dna binding protein/dna
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 35576.64

Authors

Hudson, W.H.,Rye, E.A.,Herbst, A.G.,Ortlund, E.A. (deposition date: 2015-10-09, release date: 2017-02-08, Last modification date: 2024-03-06)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.85 Å)