1pk5
From Proteopedia
OCA (Talk | contribs)
(New page: 200px<br /><applet load="1pk5" size="450" color="white" frame="true" align="right" spinBox="true" caption="1pk5, resolution 2.40Å" /> '''Crystal structure of...)
Next diff →
Revision as of 21:45, 20 November 2007
|
Crystal structure of the orphan nuclear receptor LRH-1
Overview
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.
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
Page seeded by OCA on Tue Nov 20 23:52:52 2007
