This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
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...) |
|||
| Line 1: | Line 1: | ||
| - | [[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== | ||
| Line 13: | Line 13: | ||
[[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
|
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 Thu Feb 21 14:29:43 2008
