1pk5
From Proteopedia
(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...) |
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| - | [[Image:1pk5.gif|left|200px]]<br /><applet load="1pk5" size=" | + | [[Image:1pk5.gif|left|200px]]<br /><applet load="1pk5" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1pk5, resolution 2.40Å" /> | caption="1pk5, resolution 2.40Å" /> | ||
'''Crystal structure of the orphan nuclear receptor LRH-1'''<br /> | '''Crystal structure of the orphan nuclear receptor LRH-1'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The orphan nuclear receptors SF-1 and LRH-1 are constitutively active, but | + | 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== | ==About this Structure== | ||
| - | 1PK5 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http:// | + | 1PK5 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PK5 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Fletterick, R | + | [[Category: Fletterick, R J.]] |
| - | [[Category: Ingraham, H | + | [[Category: Ingraham, H A.]] |
| - | [[Category: Krylova, I | + | [[Category: Krylova, I N.]] |
| - | [[Category: Sablin, E | + | [[Category: Sablin, E P.]] |
[[Category: ligand-binding domain]] | [[Category: ligand-binding domain]] | ||
[[Category: lrh-1]] | [[Category: lrh-1]] | ||
[[Category: nuclear receptor]] | [[Category: nuclear receptor]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:29:43 2008'' |
Revision as of 12:29, 21 February 2008
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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
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