scholarly journals Inter-residue coupling contributes to high-affinity subtype-selective binding of α-bungarotoxin to nicotinic receptors

2013 ◽  
Vol 454 (2) ◽  
pp. 311-321 ◽  
Author(s):  
Steven M. Sine ◽  
Sun Huang ◽  
Shu-Xing Li ◽  
Corrie J. B. daCosta ◽  
Lin Chen
Keyword(s):  
Crystal Structure ◽  
Ligand Binding ◽  
Nicotinic Receptors ◽  
Radioligand Binding ◽  
Binding Domain ◽  
Tyrosine Residue ◽  
Selective Binding ◽  
Conserved Residues ◽  
High Affinity ◽  
Subtype Selective

On the basis of the crystal structure of a pentameric α7 ligand-binding domain chimaera with bound α-bungarotoxin, mutagenesis and radioligand-binding measurements show that high-affinity target-selective binding depends on interactions between a single conserved tyrosine residue in α7 and nearby conserved and non-conserved residues.

Crystal structure of an ACh-binding protein reveals the ligand-binding domain of nicotinic receptors

Nature ◽  
2001 ◽  
Vol 411 (6835) ◽  
pp. 269-276 ◽  
Author(s):  
KatjuS̆a Brejc ◽  
Willem J. van Dijk ◽  
Remco V. Klaassen ◽  
Mascha Schuurmans ◽  
John van der Oost ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Ligand Binding ◽  
Nicotinic Receptors ◽  
Binding Protein ◽  
Binding Domain ◽  
Ligand Binding Domain

Crystal structure of nerve growth factor in complex with the ligand-binding domain of the TrkA receptor

Nature ◽  
10.1038/43705 ◽  
1999 ◽  
Vol 401 (6749) ◽  
pp. 184-188 ◽  
Author(s):  
Christian Wiesmann ◽  
Mark H. Ultsch ◽  
Steven H. Bass ◽  
Abraham M. de Vos
Keyword(s):  
Crystal Structure ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Ligand Binding ◽  
Binding Domain ◽  
Ligand Binding Domain ◽  
Trka Receptor ◽  
Nerve Growth

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 Crystal structure of the ligand-binding domain of the promiscuous EphA4 receptor reveals two distinct conformations

2010 ◽  
Vol 399 (4) ◽  
pp. 555-559 ◽  
Author(s):  
Nikhil Singla ◽  
Yehuda Goldgur ◽  
Kai Xu ◽  
Sari Paavilainen ◽  
Dimitar B. Nikolov ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Ligand Binding ◽  
Binding Domain ◽  
Ligand Binding Domain

How well can molecular modelling predict the crystal structure: the case of the ligand-binding domain of glutamate receptors

2000 ◽  
Vol 21 (3) ◽  
pp. 87-92 ◽  
Author(s):  
Yoav Paas ◽  
Anne Devillers-Thiéry ◽  
Vivian I Teichberg ◽  
Jean-Pierre Changeux ◽  
Miriam Eisenstein
Keyword(s):  
Crystal Structure ◽  
Ligand Binding ◽  
Glutamate Receptors ◽  
Molecular Modelling ◽  
Binding Domain ◽  
Ligand Binding Domain
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