1pk5: Difference between revisions

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[[Image:1pk5.gif|left|200px]]
{{Seed}}
[[Image:1pk5.png|left|200px]]


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{{STRUCTURE_1pk5|  PDB=1pk5  |  SCENE=  }}  
{{STRUCTURE_1pk5|  PDB=1pk5  |  SCENE=  }}  


'''Crystal structure of the orphan nuclear receptor LRH-1'''
===Crystal structure of the orphan nuclear receptor LRH-1===




==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.
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{{ABSTRACT_PUBMED_12820970}}


==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''

Revision as of 12:40, 29 July 2008

File:1pk5.png

Template:STRUCTURE 1pk5

Crystal structure of the orphan nuclear receptor LRH-1

Template:ABSTRACT PUBMED 12820970

About this Structure

1PK5 is a Single protein structure of sequence from Mus musculus. Full crystallographic information is available from OCA.

Reference

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

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