MUTATIONS IN LIVER X RECEPTOR ALPHA THAT IMPAIR DIMERIZATION AND LIGAND DEPENDENT TRANSACTIVATION.

ABSTRACT: Liver X receptor alpha (LXRα) is crucial for the maintenance of lipid and cholesterol homeostasis. Ligand binding and dimerization with retinoid X receptor (RXR) or peroxisome proliferator-activated receptor (PPAR) is required for forming active DNA binding complexes leading to gene regulation. Structure based prediction and solvent accessibility of LXRα LBD shows that residues H383, E387, H390, L414, and R415 which are located in helices 9 and 10 may be critical for mediating protein-protein interactions. In this study, LXRα interface residues were individually mutated to determine their effects on ligand binding, protein-protein association, subcellular localization, and transactivation activity. LXRα L414R and R415A lacked binding to T-0901317, but retained binding to 25-Hydroxycholeste

SUBMITTER: Bedi S 

PROVIDER: S-EPMC5630223 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature