EurekaMag
+ Most Popular
Cunninghamia lanceolata plantations in China
Mammalian lairs in paleo ecological studies and palynology
Studies on technological possibilities in utilization of anhydrous milk fat for production of recombined butter-like products
Should right-sided fibroelastomas be operated upon?
Large esophageal lipoma
Apoptosis in the mammalian thymus during normal histogenesis and under various in vitro and in vivo experimental conditions
Poissons characoides nouveaux ou non signales de l'Ilha do Bananal, Bresil
Desensitizing efficacy of Colgate Sensitive Maximum Strength and Fresh Mint Sensodyne dentifrices
Administration of fluid by subcutaneous infusion: revival of a forgotten method
Tundra mosquito control - an impossible dream?
Schizophrenia for primary care providers: how to contribute to the care of a vulnerable patient population
Geochemical pattern analysis; method of describing the Southeastern limestone regional aquifer system
Incidence of low birth weights in a hospital of Mexico City
Tabanidae
Graded management intensity of grassland systems for enhancing floristic diversity
Microbiology and biochemistry of cheese and fermented milk
The ember tetra: a new pygmy characid tetra from the Rio das Mortes, Brazil, Hyphessobrycon amandae sp. n. (Pisces, Characoidei)
Risk factors of contrast-induced nephropathy in patients after coronary artery intervention
Renovation of onsite domestic wastewater in a poorly drained soil
Observations of the propagation velocity and formation mechanism of burst fractures caused by gunshot
Systolic blood pressure in a population of infants in the first year of life: the Brompton study
Haematological studies in rats fed with metanil yellow
Studies on pasteurellosis. I. A new species of Pasteurella encountered in chronic fowl cholera
Dormancy breaking and germination of Acacia salicina Lindl. seeds
therapy of lupus nephritis. a two-year prospective study

X-ray crystal structure of the liver X receptor beta ligand binding domain: regulation by a histidine-tryptophan switch


X-ray crystal structure of the liver X receptor beta ligand binding domain: regulation by a histidine-tryptophan switch



Journal of Biological Chemistry 278(29): 27138-27143



ISSN/ISBN: 0021-9258

PMID: 12736258

DOI: 10.1074/jbc.m302260200

The x-ray crystal structures of the human liver X receptor beta ligand binding domain complexed to sterol and nonsterol agonists revealed a perpendicular histidine-tryptophan switch that holds the receptor in its active conformation. Hydrogen bonding interactions with the ligand act to position the His-435 imidazole ring against the Trp-457 indole ring, allowing an electrostatic interaction that holds the AF2 helix in the active position. The neutral oxysterol 24(S),25-epoxycholesterol accepts a hydrogen bond from His-435 that positions the imidazole ring of the histidine above the pyrrole ring of the tryptophan. In contrast, the acidic T0901317 hydroxyl group makes a shorter hydrogen bond with His-435 that pulls the imidazole over the electron-rich benzene ring of the tryptophan, possibly strengthening the electrostatic interaction. Point mutagenesis of Trp-457 supports the observation that the ligand-histidine-tryptophan coupling is different between the two ligands. The lipophilic liver X receptor ligand-binding pocket is larger than the corresponding steroid hormone receptors, which allows T0901317 to adopt two distinct conformations. These results provide a molecular basis for liver X receptor activation by a wide range of endogenous neutral and acidic ligands.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 011656898

Download citation: RISBibTeXText

Related references

X-ray Crystal Structure of the Liver X Receptor b Ligand Binding Domain. Regulation by a Histidine-Tryptophan Switch. The Journal of Biological Chemistry 278(29): 138-43, 2003

Crystal structure of the human liver X receptor beta ligand-binding domain in complex with a synthetic agonist. Journal of Molecular Biology 334(5): 853-861, 2003

The 1.1 A crystal structure of human TGF-beta type II receptor ligand binding domain. Structure 10(7): 913-919, 2002

Crystal Structure of the Human Liver X Receptor b Ligand-binding Domain in Complex with a Synthetic Agonist. Journal of Molecular Biology 334(5): 3-61, 2003

Homology modelling of the nuclear receptors: human oestrogen receptorbeta (hERbeta), the human pregnane-X-receptor (PXR), the Ah receptor (AhR) and the constitutive androstane receptor (CAR) ligand binding domains from the human oestrogen receptor alpha (hERalpha) crystal structure, and the human peroxisome proliferator activated receptor alpha (PPARalpha) ligand binding domain from the human PPARgamma crystal structure. Journal of Steroid Biochemistry and Molecular Biology 84(2-3): 117-132, 2003

Homology modelling of the nuclear receptors Human oestrogen receptorbeta , the human pregnane-X-receptor , the Ah receptor and the constitutive androstane receptor ligand binding domains from the human oestrogen receptor alpha crystal structure, and the human peroxisome proliferator activated receptor alpha ligand binding domain from the human PPARgamma crystal structure. Journal of Steroid Biochemistry and Molecular Biology 84(2-3): 117-132, 2003

Homology modelling of the oestrogen receptor beta ligand binding domain from the human oestrogen receptor alpha crystal structure. Toxicology Letters (Shannon) 116(Suppl 1): 58-59, September 1st, 2000

A modified oestrogen receptor ligand-binding domain as an improved switch for the regulation of heterologous proteins. Nucleic Acids Research 23(10): 1686-1690, 1995

Crystal structure of the T877A human androgen receptor ligand-binding domain complexed to cyproterone acetate provides insight for ligand-induced conformational changes and structure-based drug design. Journal of Biological Chemistry 282(18): 13648-13655, 2007

Effects of co-expression of liver X receptor β-ligand binding domain with its partner, retinoid X receptor α-ligand binding domain, on their solubility and biological activity in Escherichia coli. Journal of Microbiology and Biotechnology 25(2): 247-254, 2015

Crystal structure of human lectin-like, oxidized low-density lipoprotein receptor 1 ligand binding domain and its ligand recognition mode to OxLDL. Structure 13(6): 905-917, 2005

The 1.1 Crystal Structure of Human Tgf- Type Ii Receptor Ligand Binding Domain. Structure 10(7): 913-919, 2002

Crystal structure of the ligand-binding domain of the human nuclear receptor RXR-α. Nature (London) 375(6530): 377-382, 1995

Evidence for Ligand-independent Transcriptional Activation of the Human Estrogen-related Receptor a (ERRa). Crystal Structure of ERRa Ligand Binding Domain in Complex with Peroxisome Proliferator-activated Receptor Coactivor-1a. Journal of Biological Chemistry 279(47): 330-337, 2004

Allosteric binding site in a Cys-loop receptor ligand-binding domain unveiled in the crystal structure of ELIC in complex with chlorpromazine. Proceedings of the National Academy of Sciences of the United States of America 113(43): E6696-E6703, 2016