共查询到20条相似文献,搜索用时 15 毫秒
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Structural analyses reveal phosphatidyl inositols as ligands for the NR5 orphan receptors SF-1 and LRH-1 总被引:32,自引:0,他引:32
Krylova IN Sablin EP Moore J Xu RX Waitt GM MacKay JA Juzumiene D Bynum JM Madauss K Montana V Lebedeva L Suzawa M Williams JD Williams SP Guy RK Thornton JW Fletterick RJ Willson TM Ingraham HA 《Cell》2005,120(3):343-355
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Freeman LA Kennedy A Wu J Bark S Remaley AT Santamarina-Fojo S Brewer HB 《Journal of lipid research》2004,45(7):1197-1206
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Liver receptor homolog-1 regulates bile acid homeostasis but is not essential for feedback regulation of bile acid synthesis 总被引:2,自引:0,他引:2
Lee YK Schmidt DR Cummins CL Choi M Peng L Zhang Y Goodwin B Hammer RE Mangelsdorf DJ Kliewer SA 《Molecular endocrinology (Baltimore, Md.)》2008,22(6):1345-1356
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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
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Molecular basis for feedback regulation of bile acid synthesis by nuclear receptors 总被引:22,自引:0,他引:22
Lu TT Makishima M Repa JJ Schoonjans K Kerr TA Auwerx J Mangelsdorf DJ 《Molecular cell》2000,6(3):507-515