PDBsum entry 4hn5

Transcription/DNA

PDB id: 4hn5

Contents

Protein chains

72 a.a.

DNA/RNA

Metals

_ZN ×4

Waters ×162

PDB id:

4hn5

Name:

Transcription/DNA

Title:

Gr DNA binding domain - tslp ngre complex

Structure:

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

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: nr3c1, grl. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Synthetic construct. Organism_taxid: 32630.

Resolution:

1.90Å R-factor: 0.209 R-free: 0.235

Authors:

W.H.Hudson,C.E.Youn,E.A.Ortlund

Key ref:

W.H.Hudson et al. (2013). The structural basis of direct glucocorticoid-mediated transrepression. Nat Struct Biol, 20, 53-58. PubMed id: 23222642

Date:

18-Oct-12 Release date: 12-Dec-12

Protein chains

P04150  (GCR_HUMAN) -  Glucocorticoid receptor from Homo sapiens

Seq: 777 a.a.

Struc: 72 a.a.

DNA/RNA chains

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

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

Enzyme reactions

• Enzyme class: E.C.?

Nat Struct Biol 20:53-58 (2013)

PubMed id: 23222642

The structural basis of direct glucocorticoid-mediated transrepression.

W.H.Hudson, C.Youn, E.A.Ortlund.

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.