共查询到20条相似文献,搜索用时 15 毫秒
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Willson TM 《Structure (London, England : 1993)》2002,10(12):1605-1606
A high-resolution X-ray crystal structure of the retinoic acid receptor-related orphan receptor (RORalpha; NR1F1), which reveals a molecule of cholesterol within the ligand binding pocket, is a breakthrough in functional analysis of this orphan nuclear receptor. 相似文献
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The 2.7 A X-ray crystal structure of the DNA-binding domain (DBD) of the orphan nuclear receptor, nerve growth factor-induced-B (NGFI-B), complexed to its high-affinity DNA target, represents the first structure analysis of a nuclear receptor DBD bound as a monomer to DNA. The structure of the core DBD and its interactions with the major groove of the DNA are similar to previously crystallographically solved DBD-DNA complexes in this superfamily; however, residues C-terminal to this core form a separate and unique substructure that interacts extensively and in a sequence-specific way with the minor groove of its DNA target, in particular with the characteristic 3 A-T base-pair identity element that extends 5' to the usual nuclear receptor half-site (AGGTCA). 相似文献
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Besnard S Heymes C Merval R Rodriguez M Galizzi JP Boutin JA Mariani J Tedgui A 《FEBS letters》2002,511(1-3):36-40
Retinoic acid receptor-related orphan receptor alpha (RORalpha) is a member of the nuclear receptor superfamily. Using RT-PCR, RORalpha mRNA was identified in human aortic smooth muscle cells (hASMC), endothelial cells (EC), as well as in human mammary arteries and atherosclerotic plaques. We found a predominant expression of RORalpha1 in hASMC, and RORalpha4 in EC. RORalpha2 and RORalpha3 were not detected. In arteries, RORalpha4 was predominant compared with RORalpha1. In atherosclerotic plaques, RORalpha expression was significantly decreased. In hASMC stimulated with cytokines, RORalpha expression was increased by 2.5-fold. RORalpha mRNA was also significantly increased (approximately 2-fold) in hASMC and EC cultured under hypoxia. 相似文献
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Song KH Park YY Park KC Hong CY Park JH Shong M Lee K Choi HS 《Molecular endocrinology (Baltimore, Md.)》2004,18(8):1929-1940
DAX-1 (dosage-sensitive sex reversal adrenal hypoplasia congenital critical region on the X chromosome, gene 1) (NROB1) is an atypical member of the nuclear receptor family, which lacks the classical zinc finger DNA binding domain and acts as a coregulator of a number of nuclear receptors. In this study, we have found that DAX-1 is a novel coregulator of the orphan nuclear receptor Nur77 (NR4A1). We demonstrate that DAX-1 represses the Nur77 transactivation by transient transfection assays. Specific interaction between Nur77 and DAX-1 was detected by coimmunoprecipitation, yeast two-hybrid, and glutathione-S-transferase pull-down assays. The ligand binding domain of DAX-1 and the activation function-2 domain of Nur77 were determined as the direct interaction domains between DAX-1 and Nur77. In vitro competition binding assay showed that DAX-1 repressed Nur77 transactivation through the competition with steroid receptor coactivator-1 for the binding of Nur77. Moreover, DAX-1 repressed Nur77- and LH-dependent increase of cytochrome P450 protein 17 promoter activity in transient transfection assays. Furthermore, Nur77-mediated transactivation was significantly increased by down-regulation of DAX-1 expression with DAX-1 small interfering RNA in testicular Leydig cell line, K28. LH treatment induced a transient increase in Nur77 mRNA, whereas LH repressed DAX-1 expression in a time- and dose-dependent manner in K28 cells. In addition, immunohistochemical analysis showed the expression of Nur77 in mouse testicular Leydig cells. These results suggest that DAX-1 acts as a novel coregulator of the orphan nuclear receptor Nur77, and that the DAX-1 may play a key role in the regulation of Nur77-mediated steroidogenesis in testicular Leydig cells. 相似文献
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Zhou XE Suino-Powell KM Xu Y Chan CW Tanabe O Kruse SW Reynolds R Engel JD Xu HE 《The Journal of biological chemistry》2011,286(4):2877-2885
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Akt inhibits the orphan nuclear receptor Nur77 and T-cell apoptosis. 总被引:12,自引:0,他引:12
N Masuyama K Oishi Y Mori T Ueno Y Takahama Y Gotoh 《The Journal of biological chemistry》2001,276(35):32799-32805
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Raspè E Mautino G Duval C Fontaine C Duez H Barbier O Monte D Fruchart J Fruchart JC Staels B 《The Journal of biological chemistry》2002,277(51):49275-49281
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Structural basis for ligand-independent activation of the orphan nuclear receptor LRH-1 总被引:2,自引:0,他引:2
The orphan nuclear receptors SF-1 and LRH-1 are constitutively active, but it remains uncertain whether their activation is hormone dependent. We report the crystal structure of the LRH-1 ligand binding domain to 2.4 A resolution and find the receptor to be a monomer that adopts an active conformation with a large but empty hydrophobic pocket. Adding bulky side chains into this pocket resulted in full or greater activity suggesting that, while LRH-1 could accommodate potential ligands, these are dispensable for basal activity. Constitutive LRH-1 activity appears to be conferred by a distinct structural element consisting of an extended helix 2 that provides an additional layer to the canonical LBD fold. Mutating the conserved arginine in helix 2 reduced LRH-1 receptor activity and coregulator recruitment, consistent with the partial loss-of-function phenotype exhibited by an analogous SF-1 human mutant. These findings illustrate an alternative structural strategy for nuclear receptor stabilization in the absence of ligand binding. 相似文献