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J Steroid Biochem Mol Biol
2008 May 01;1101-2:83-94. doi: 10.1016/j.jsbmb.2008.02.007.
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Ligand specificity and evolution of liver X receptors.
Reschly EJ
,
Ai N
,
Welsh WJ
,
Ekins S
,
Hagey LR
,
Krasowski MD
.
???displayArticle.abstract??? Liver X receptors (LXRs) are key regulators of lipid and cholesterol metabolism in mammals. Little is known, however, about the function and evolution of LXRs in non-mammalian species. The present study reports the cloning of LXRs from African clawed frog (Xenopus laevis), Western clawed frog (Xenopus tropicalis), and zebrafish (Danio rerio), and their functional characterization and comparison with human and mouse LXRs. Additionally, an ortholog of LXR in the chordate invertebrate Ciona intestinalis was cloned and functionally characterized. Ligand specificities of the frog and zebrafish LXRs were very similar to LXRalpha and LXRbeta from human and mouse. All vertebrate LXRs studied were activated robustly by the synthetic ligands T-0901317 and GW3965 and by a variety of oxysterols. In contrast, Ciona LXR was not activated by T-0901317 or GW3965 but was activated by a limited number of oxysterols, as well as some androstane and pregnane steroids. Pharmacophore analysis, homology modeling, and docking studies of Ciona LXR predict a receptor with a more restricted ligand-binding pocket and less intrinsic disorder in the ligand-binding domain compared to vertebrate LXRs. The results suggest that LXRs have a long evolutionary history, with vertebrate LXRs diverging from invertebrate LXRs in ligand specificity.
Anderson,
A more detailed study of bile salt evolution, including techniques for small-scale identification and their application to amphibian biles.
1974, Pubmed,
Xenbase
Anderson,
A more detailed study of bile salt evolution, including techniques for small-scale identification and their application to amphibian biles.
1974,
Pubmed
,
Xenbase
Bramlett,
A natural product ligand of the oxysterol receptor, liver X receptor.
2003,
Pubmed
Collins,
Identification of a nonsteroidal liver X receptor agonist through parallel array synthesis of tertiary amines.
2002,
Pubmed
Delrio,
Identification and biosynthesis of steroid hormones in the gonads of Ciona intestinalis.
1971,
Pubmed
Delsuc,
Tunicates and not cephalochordates are the closest living relatives of vertebrates.
2006,
Pubmed
Dunker,
Flexible nets. The roles of intrinsic disorder in protein interaction networks.
2005,
Pubmed
Ekins,
A ligand-based approach to understanding selectivity of nuclear hormone receptors PXR, CAR, FXR, LXRalpha, and LXRbeta.
2002,
Pubmed
Ekins,
Human pregnane X receptor antagonists and agonists define molecular requirements for different binding sites.
2007,
Pubmed
Farber,
Genetic analysis of digestive physiology using fluorescent phospholipid reporters.
2001,
Pubmed
Färnegårdh,
The three-dimensional structure of the liver X receptor beta reveals a flexible ligand-binding pocket that can accommodate fundamentally different ligands.
2003,
Pubmed
Goldstone,
The chemical defensome: environmental sensing and response genes in the Strongylocentrotus purpuratus genome.
2006,
Pubmed
Goto,
Physicochemical and physiological properties of 5alpha-cyprinol sulfate, the toxic bile salt of cyprinid fish.
2003,
Pubmed
Hoerer,
Crystal structure of the human liver X receptor beta ligand-binding domain in complex with a synthetic agonist.
2003,
Pubmed
Janowski,
Structural requirements of ligands for the oxysterol liver X receptors LXRalpha and LXRbeta.
1999,
Pubmed
Janowski,
An oxysterol signalling pathway mediated by the nuclear receptor LXR alpha.
1996,
Pubmed
Jaye,
Discovery of substituted maleimides as liver X receptor agonists and determination of a ligand-bound crystal structure.
2005,
Pubmed
Jones,
Development and validation of a genetic algorithm for flexible docking.
1997,
Pubmed
Kalaany,
LXRS and FXR: the yin and yang of cholesterol and fat metabolism.
2006,
Pubmed
Krasowski,
Evolutionary selection across the nuclear hormone receptor superfamily with a focus on the NR1I subfamily (vitamin D, pregnane X, and constitutive androstane receptors).
2005,
Pubmed
,
Xenbase
Krasowski,
Evolution of the pregnane x receptor: adaptation to cross-species differences in biliary bile salts.
2005,
Pubmed
,
Xenbase
Lehmann,
Activation of the nuclear receptor LXR by oxysterols defines a new hormone response pathway.
1997,
Pubmed
Liang,
Anatomy of protein pockets and cavities: measurement of binding site geometry and implications for ligand design.
1998,
Pubmed
Maglich,
The first completed genome sequence from a teleost fish (Fugu rubripes) adds significant diversity to the nuclear receptor superfamily.
2003,
Pubmed
Moschetta,
A phylogenetic survey of biliary lipids in vertebrates.
2005,
Pubmed
Motola,
Identification of ligands for DAF-12 that govern dauer formation and reproduction in C. elegans.
2006,
Pubmed
Mouzat,
Oxysterol nuclear receptor LXRbeta regulates cholesterol homeostasis and contractile function in mouse uterus.
2007,
Pubmed
Peng,
Optimizing long intrinsic disorder predictors with protein evolutionary information.
2005,
Pubmed
Rannug,
Certain photooxidized derivatives of tryptophan bind with very high affinity to the Ah receptor and are likely to be endogenous signal substances.
1987,
Pubmed
Rossi,
High pressure liquid chromatographic analysis of conjugated bile acids in human bile: simultaneous resolution of sulfated and unsulfated lithocholyl amidates and the common conjugated bile acids.
1987,
Pubmed
Schultz,
Role of LXRs in control of lipogenesis.
2000,
Pubmed
Seo,
FOR, a novel orphan nuclear receptor related to farnesoid X receptor.
2002,
Pubmed
,
Xenbase
Song,
Cholestenoic acid is a naturally occurring ligand for liver X receptor alpha.
2000,
Pubmed
Song,
Selective activation of liver X receptor alpha by 6alpha-hydroxy bile acids and analogs.
2000,
Pubmed
Song,
Ubiquitous receptor: a receptor that modulates gene activation by retinoic acid and thyroid hormone receptors.
1994,
Pubmed
Steinmetz,
Binding of ligands and activation of transcription by nuclear receptors.
2001,
Pubmed
Svensson,
Crystal structure of the heterodimeric complex of LXRalpha and RXRbeta ligand-binding domains in a fully agonistic conformation.
2003,
Pubmed
Thornton,
Resurrecting the ancestral steroid receptor: ancient origin of estrogen signaling.
2003,
Pubmed
Une,
Natural occurrence and chemical synthesis of bile alcohols, higher bile acids, and short side chain bile acids.
1994,
Pubmed
Voogt,
On the sterols of some ascidians.
1975,
Pubmed
Williams,
X-ray crystal structure of the liver X receptor beta ligand binding domain: regulation by a histidine-tryptophan switch.
2003,
Pubmed
Yagi,
A genomewide survey of developmentally relevant genes in Ciona intestinalis. III. Genes for Fox, ETS, nuclear receptors and NFkappaB.
2003,
Pubmed
Yoshida,
A chemoattractant for ascidian spermatozoa is a sulfated steroid.
2002,
Pubmed
