The important role of residue F268 in ligand binding by LXRbeta.

Détails

ID Serval
serval:BIB_542D46A25AC0
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
The important role of residue F268 in ligand binding by LXRbeta.
Périodique
Febs Letters
Auteur(s)
Urban F., Cavazos G., Dunbar J., Tan B., Escher P., Tafuri S., Wang M.
ISSN
0014-5793 (Print)
ISSN-L
0014-5793
Statut éditorial
Publié
Date de publication
2000
Peer-reviewed
Oui
Volume
484
Numéro
2
Pages
159-163
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
Liver X receptors (LXRs) are nuclear receptors that regulate the metabolism of cholesterol and bile acids. Despite information on the specificity of their natural ligands, oxysterols, relatively little is known about the ligand binding site in LXRs. The helix 3 region in the ligand binding domain (LBD) of peroxisome proliferator-activated receptors (PPARs) has been implicated in ligand entry. Sequence alignment of LXRs, farnesoid X receptor (FXR), and PPARs identified the corresponding helix 3 region in the LXRbeta LBD. Residues F268 and T272, which are conserved in all the aligned sequences and only in LXRs and FXR, respectively, were replaced with alanine. The effects of these mutations on ligand binding and receptor activation were examined using an in vitro ligand binding assay and a cell based reporter assay, respectively. The LXRbeta mutant F268A did not bind ligand. In contrast, conversion of T272 to alanine has no effect on ligand binding. By transiently expressing a chimeric receptor containing Escherichia coli tetracycline repressor (TetR) and LXRbeta LBD and a reporter with a TetR binding site, we show that mutant F268A lost the ability to activate transcription of the reporter, whereas mutant T272A still has an activity similar to that of the wild-type LXRbeta. These data, consistent with the findings in the in vitro ligand binding assay and our 3D modeling, are the first study that identifies a residue critical for ligand binding in LXRbeta.
Mots-clé
Amino Acid Sequence, Animals, Binding Sites, CHO Cells, Cricetinae, DNA-Binding Proteins, Ligands, Models, Molecular, Molecular Sequence Data, Mutagenesis, Orphan Nuclear Receptors, Phenylalanine/genetics, Phenylalanine/metabolism, Protein Conformation, Receptors, Cytoplasmic and Nuclear/chemistry, Receptors, Cytoplasmic and Nuclear/genetics, Recombinant Fusion Proteins/metabolism, Sequence Homology, Amino Acid, Transcription Factors/chemistry, Transcriptional Activation
Pubmed
Création de la notice
28/02/2015 22:25
Dernière modification de la notice
20/08/2019 14:09
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