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| [[Image:1pk5.gif|left|200px]] | | {{Seed}} |
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| {{STRUCTURE_1pk5| PDB=1pk5 | SCENE= }} | | {{STRUCTURE_1pk5| PDB=1pk5 | SCENE= }} |
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| '''Crystal structure of the orphan nuclear receptor LRH-1'''
| | ===Crystal structure of the orphan nuclear receptor LRH-1=== |
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| ==Overview==
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| 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. | | The line below this paragraph, {{ABSTRACT_PUBMED_12820970}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 12820970 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_12820970}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Lrh-1]] | | [[Category: Lrh-1]] |
| [[Category: Nuclear receptor]] | | [[Category: Nuclear receptor]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 05:10:52 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 15:40:13 2008'' |
