scholarly journals The Structure of a High-Affinity Kainate Receptor: GluK4 Ligand-Binding Domain Crystallized with Kainate

Structure ◽  
2016 ◽  
Vol 24 (9) ◽  
pp. 1582-1589 ◽  
Author(s):  
Ole Kristensen ◽  
Lise Baadsgaard Kristensen ◽  
Stine Møllerud ◽  
Karla Frydenvang ◽  
Darryl S. Pickering ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Binding Domain ◽  
Ligand Binding Domain ◽  
Kainate Receptor ◽  
High Affinity

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.

scholarly journals Stability of ligand-binding domain dimer assembly controls kainate receptor desensitization

2009 ◽  
Vol 28 (10) ◽  
pp. 1518-1530 ◽  
Author(s):  
Charu Chaudhry ◽  
Matthew C Weston ◽  
Peter Schuck ◽  
Christian Rosenmund ◽  
Mark L Mayer
Keyword(s):  
Ligand Binding ◽  
Binding Domain ◽  
Ligand Binding Domain ◽  
Kainate Receptor ◽  
Receptor Desensitization

scholarly journals High Conformational Variability in the GluK2 Kainate Receptor Ligand-Binding Domain

Structure ◽  
2019 ◽  
Vol 27 (1) ◽  
pp. 189-195.e2 ◽  
Author(s):  
Tyler J. Wied ◽  
Alfred C. Chin ◽  
Albert Y. Lau
Keyword(s):  
Ligand Binding ◽  
Binding Domain ◽  
Ligand Binding Domain ◽  
Kainate Receptor ◽  
Receptor Ligand ◽  
Conformational Variability

Molecular Recognition of Two 2,4-syn-Functionalized (S)-Glutamate Analogues by the Kainate Receptor GluK3 Ligand Binding Domain

ChemMedChem ◽  
2014 ◽  
Vol 9 (10) ◽  
pp. 2254-2259 ◽  
Author(s):  
Raminta Venskutonytė ◽  
Anja P. Larsen ◽  
Karla Frydenvang ◽  
Michael Gajhede ◽  
Emmanuelle Sagot ◽  
...  
Keyword(s):  
Molecular Recognition ◽  
Ligand Binding ◽  
Binding Domain ◽  
Ligand Binding Domain ◽  
Kainate Receptor ◽  
Glutamate Analogues

scholarly journals Novel FXXFF and FXXMF Motifs in Androgen Receptor Cofactors Mediate High Affinity and Specific Interactions with the Ligand-binding Domain

2006 ◽  
Vol 281 (28) ◽  
pp. 19407-19416 ◽  
Author(s):  
Dennis J. van de Wijngaart ◽  
Martin E. van Royen ◽  
Remko Hersmus ◽  
Ashley C. W. Pike ◽  
Adriaan B. Houtsmuller ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Ligand Binding ◽  
Binding Domain ◽  
Ligand Binding Domain ◽  
Specific Interactions ◽  
High Affinity
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