1pk5

Crystal structure of the orphan nuclear receptor LRH-1

spinqualitylabelsall models 1pk5, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1pk5 is a 2 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.4Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function NR5A2_MOUSE Binds to promoters containing the sequence element 5'-AACGACCGACCTTGAG-3'. Plays a role in the regulation of gene expression in liver and pancreas. May play a role in embryonic development (By similarity). Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed 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. Structural basis for ligand-independent activation of the orphan nuclear receptor LRH-1.,Sablin EP, Krylova IN, Fletterick RJ, Ingraham HA Mol Cell. 2003 Jun;11(6):1575-85. PMID:12820970 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Liver receptor homolog-1

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