Backbone dynamics of the glucocorticoid receptor DNA-binding domain. [Erratum to document cited in CA117(25):245708z]

Biochemistry ◽  
1993 ◽  
Vol 32 (14) ◽  
pp. 3829-3829
Author(s):  
Helena Berglund ◽  
Helena Kovacs ◽  
Karin Dahlman-Wright ◽  
Jan Aake Gustafsson ◽  
Torleif Haerd
Keyword(s):  
Dna Binding ◽  
Glucocorticoid Receptor ◽  
Binding Domain ◽  
Backbone Dynamics ◽  
Dna Binding Domain

Backbone dynamics of the glucocorticoid receptor DNA-binding domain

Biochemistry ◽  
1992 ◽  
Vol 31 (48) ◽  
pp. 12001-12011 ◽  
Author(s):  
Helena Berglund ◽  
Helena Kovacs ◽  
Karin Dahlman-Wright ◽  
Jan Aake Gustafsson ◽  
Torleif Haerd
Keyword(s):  
Dna Binding ◽  
Glucocorticoid Receptor ◽  
Binding Domain ◽  
Backbone Dynamics ◽  
Dna Binding Domain

scholarly journals Structure refinement of the glucocorticoid receptor-DNA binding domain from NMR data by relaxation matrix calculations

1995 ◽  
Vol 247 (4) ◽  
pp. 689-700 ◽  
Author(s):  
Marc A.A. van Tilborg ◽  
Alexandre M.J.J. Bonvin ◽  
Karl Hård ◽  
Adrian L. Davis ◽  
Bonnie Maler ◽  
...  
Keyword(s):  
Dna Binding ◽  
Glucocorticoid Receptor ◽  
Structure Refinement ◽  
Binding Domain ◽  
Dna Binding Domain ◽  
Relaxation Matrix ◽  
Nmr Data

Structure and Dynamics of the Glucocorticoid Receptor DNA-Binding Domain:  Comparison of Wild Type and a Mutant with Altered Specificity†

Biochemistry ◽  
1997 ◽  
Vol 36 (37) ◽  
pp. 11188-11197 ◽  
Author(s):  
Helena Berglund ◽  
Magnus Wolf-Watz ◽  
Thomas Lundbäck ◽  
Susanne van den Berg ◽  
Torleif Härd
Keyword(s):  
Dna Binding ◽  
Glucocorticoid Receptor ◽  
Binding Domain ◽  
Dna Binding Domain ◽  
Wild Type ◽  
Structure And Dynamics

scholarly journals Molecular Determinants of Glucocorticoid Receptor Mobility in Living Cells: the Importance of Ligand Affinity

2003 ◽  
Vol 23 (6) ◽  
pp. 1922-1934 ◽  
Author(s):  
Marcel J. M. Schaaf ◽  
John A. Cidlowski
Keyword(s):  
Dna Binding ◽  
Glucocorticoid Receptor ◽  
Ligand Binding ◽  
Conformational Change ◽  
Binding Domain ◽  
Ligand Binding Domain ◽  
Dependent Manner ◽  
Dna Binding Domain ◽  
Ligand Affinity ◽  
High Affinity

ABSTRACT The actions of glucocorticoids are mediated by the glucocorticoid receptor (GR), which is activated upon ligand binding, and can alter the expression of target genes either by transrepression or transactivation. We have applied FRAP (fluorescence recovery after photobleaching) to quantitatively assess the mobility of the yellow fluorescent protein (YFP)-tagged human GR α-isoform (hGRα) in the nucleus of transiently transfected COS-1 cells and to elucidate determinants of its mobility. Addition of the high-affinity agonist dexamethasone markedly decreases the mobility of the receptor in a concentration-dependent manner, whereas low-affinity ligands like corticosterone decrease the mobility to a much lesser extent. Analysis of other hGRα ligands differing in affinity suggests that it is the affinity of the ligand that is a major determinant of the decrease in mobility. Similar results were observed for two hGRα antagonists, the low-affinity antagonist ZK98299 and the high-affinity antagonist RU486. The effect of ligand affinity on mobility was confirmed with the hGRα mutant Q642V, which has an altered affinity for triamcinolone acetonide, dexamethasone, and corticosterone. Analysis of hGRα deletion mutants indicates that both the DNA-binding domain and the ligand-binding domain of the receptor are required for a maximal ligand-induced decrease in receptor mobility. Interestingly, the mobility of transfected hGRα differs among cell types. Finally, the proteasome inhibitor MG132 immobilizes a subpopulation of unliganded receptors, via a mechanism requiring the DNA-binding domain and the N-terminal part of the ligand-binding domain. Ligand binding makes the GR resistant to the immobilizing effect of MG132, and this effect depends on the affinity of the ligand. Our data suggest that ligand binding induces a conformational change of the receptor which is dependent on the affinity of the ligand. This altered conformation decreases the mobility of the receptor, probably by targeting the receptor to relatively immobile nuclear domains with which it transiently associates. In addition, this conformational change blocks immobilization of the receptor by MG132.

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