PDBsum entry 5e6c

DNA binding protein/DNA

PDB id: 5e6c

Contents

Protein chains

78 a.a.

72 a.a.

DNA/RNA

Metals

_ZN ×4

Waters ×29

PDB id:

5e6c

Name:

DNA binding protein/DNA

Title:

Glucocorticoid receptor DNA binding domain - ccl2 nf-kb response element complex

Structure:

Glucocorticoid receptor. Chain: a, b. Fragment: unp residues 391-480. Synonym: gr,nuclear receptor subfamily 3 group c member 1. Engineered: yes. DNA (5'-d( Ap Gp Tp Gp Gp Ap Ap Ap Tp Tp Cp Cp Cp Ap Cp T)- 3'). Chain: c. Engineered: yes.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: nr3c1, grl. Expressed in: escherichia coli. Expression_system_taxid: 469008. Synthetic: yes. Organism_taxid: 9606

Resolution:

2.20Å R-factor: 0.237 R-free: 0.271

Authors:

W.H.Hudson,E.A.Rye,A.G.Herbst,E.A.Ortlund

Key ref:

W.H.Hudson et al. (2018). Cryptic glucocorticoid receptor-binding sites pervade genomic NF-κB response elements. Nat Commun, 9, 1337. PubMed id: 29626214

Date:

09-Oct-15 Release date: 08-Feb-17

Protein chain

P04150  (GCR_HUMAN) -  Glucocorticoid receptor from Homo sapiens

Seq: 777 a.a.

Struc: 78 a.a.

Protein chain

P04150  (GCR_HUMAN) -  Glucocorticoid receptor from Homo sapiens

Seq: 777 a.a.

Struc: 72 a.a.

DNA/RNA chains

A-G-T-G-G-A-A-A-T-T-C-C-C-A-C-T 16 bases

A-G-T-G-G-G-A-A-T-T-T-C-C-A-C-T 16 bases

Enzyme reactions

• Enzyme class: Chains A, B: E.C.?

Nat Commun 9:1337 (2018)

PubMed id: 29626214

Cryptic glucocorticoid receptor-binding sites pervade genomic NF-κB response elements.

W.H.Hudson, I.M.S.Vera, J.C.Nwachukwu, E.R.Weikum, A.G.Herbst, Q.Yang, D.L.Bain, K.W.Nettles, D.J.Kojetin, E.A.Ortlund.

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.