4HN6

GR DNA Binding Domain R460D/D462R - TSLP nGRE Complex

Summary for 4HN6

• Entry DOI: 10.2210/pdb4hn6/pdb
• Related: 4HN5
• Descriptor: Glucocorticoid receptor, DNA (5'-D(*CP*GP*CP*CP*TP*CP*CP*GP*GP*GP*AP*GP*AP*GP*CP*T)-3'), DNA (5'-D(*AP*GP*CP*TP*CP*TP*CP*CP*CP*GP*GP*AP*GP*GP*CP*G)-3'), ... (5 entities in total)
• Functional Keywords: glucocorticoid receptor, steroid receptors, dna, ngre, repression, transcription, transcription-dna complex, transcription/dna
• Biological source: Homo sapiens (human); More
• Cellular location: Isoform Alpha: Cytoplasm . Isoform Beta: Nucleus . Isoform Alpha-B: Nucleus : P04150
• Total number of polymer chains: 4
• Total formula weight: 35581.58

Authors

Hudson, W.H.,Youn, C.E.,Ortlund, E.A. (deposition date: 2012-10-18, release date: 2012-12-12, Last modification date: 2024-02-28)

Primary citation

Hudson, W.H.,Youn, C.,Ortlund, E.A.
The structural basis of direct glucocorticoid-mediated transrepression.
Nat.Struct.Mol.Biol., 20:53-58, 2013

PubMed Abstract: A newly discovered negative glucocorticoid response element (nGRE) mediates DNA-dependent transrepression by the glucocorticoid receptor (GR) across the genome and has a major role in immunosuppressive therapy. The nGRE differs dramatically from activating response elements, and the mechanism driving GR binding and transrepression is unknown. To unravel the mechanism of nGRE-mediated transrepression by the GR, we characterized the interaction between GR and an nGRE in the thymic stromal lymphopoietin (TSLP) promoter. We show using structural and mechanistic approaches that nGRE binding is a new mode of sequence recognition by human GR and that nGREs prevent receptor dimerization through a unique GR-binding orientation and strong negative cooperativity, ensuring the presence of monomeric GR at repressive elements.

PubMed: 23222642
DOI: 10.1038/nsmb.2456

Experimental method

X-RAY DIFFRACTION (2.549 Å)