1ovl
From Proteopedia
(New page: 200px<br /> <applet load="1ovl" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ovl, resolution 2.2Å" /> '''Crystal Structure of...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:1ovl.gif|left|200px]]<br /> | + | [[Image:1ovl.gif|left|200px]]<br /><applet load="1ovl" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1ovl" size=" | + | |
caption="1ovl, resolution 2.2Å" /> | caption="1ovl, resolution 2.2Å" /> | ||
'''Crystal Structure of Nurr1 LBD'''<br /> | '''Crystal Structure of Nurr1 LBD'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Members of the nuclear receptor (NR) superfamily of transcription factors | + | Members of the nuclear receptor (NR) superfamily of transcription factors modulate gene transcription in response to small lipophilic molecules. Transcriptional activity is regulated by ligands binding to the carboxy-terminal ligand-binding domains (LBDs) of cognate NRs. A subgroup of NRs referred to as 'orphan receptors' lack identified ligands, however, raising issues about the function of their LBDs. Here we report the crystal structure of the LBD of the orphan receptor Nurr1 at 2.2 A resolution. The Nurr1 LBD adopts a canonical protein fold resembling that of agonist-bound, transcriptionally active LBDs in NRs, but the structure has two distinctive features. First, the Nurr1 LBD contains no cavity as a result of the tight packing of side chains from several bulky hydrophobic residues in the region normally occupied by ligands. Second, Nurr1 lacks a 'classical' binding site for coactivators. Despite these differences, the Nurr1 LBD can be regulated in mammalian cells. Notably, transcriptional activity is correlated with the Nurr1 LBD adopting a more stable conformation. Our findings highlight a unique structural class of NRs and define a model for ligand-independent NR function. |
==Disease== | ==Disease== | ||
| Line 11: | Line 10: | ||
==About this Structure== | ==About this Structure== | ||
| - | 1OVL is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with K, BR and IOD as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1OVL is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=K:'>K</scene>, <scene name='pdbligand=BR:'>BR</scene> and <scene name='pdbligand=IOD:'>IOD</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OVL OCA]. |
==Reference== | ==Reference== | ||
| Line 26: | Line 25: | ||
[[Category: nuur1]] | [[Category: nuur1]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:22:03 2008'' |
Revision as of 12:22, 21 February 2008
|
Crystal Structure of Nurr1 LBD
Contents |
Overview
Members of the nuclear receptor (NR) superfamily of transcription factors modulate gene transcription in response to small lipophilic molecules. Transcriptional activity is regulated by ligands binding to the carboxy-terminal ligand-binding domains (LBDs) of cognate NRs. A subgroup of NRs referred to as 'orphan receptors' lack identified ligands, however, raising issues about the function of their LBDs. Here we report the crystal structure of the LBD of the orphan receptor Nurr1 at 2.2 A resolution. The Nurr1 LBD adopts a canonical protein fold resembling that of agonist-bound, transcriptionally active LBDs in NRs, but the structure has two distinctive features. First, the Nurr1 LBD contains no cavity as a result of the tight packing of side chains from several bulky hydrophobic residues in the region normally occupied by ligands. Second, Nurr1 lacks a 'classical' binding site for coactivators. Despite these differences, the Nurr1 LBD can be regulated in mammalian cells. Notably, transcriptional activity is correlated with the Nurr1 LBD adopting a more stable conformation. Our findings highlight a unique structural class of NRs and define a model for ligand-independent NR function.
Disease
Known diseases associated with this structure: Parkinson disease OMIM:[601828]
About this Structure
1OVL is a Protein complex structure of sequences from Homo sapiens with , and as ligands. Full crystallographic information is available from OCA.
Reference
Structure and function of Nurr1 identifies a class of ligand-independent nuclear receptors., Wang Z, Benoit G, Liu J, Prasad S, Aarnisalo P, Liu X, Xu H, Walker NP, Perlmann T, Nature. 2003 May 29;423(6939):555-60. PMID:12774125
Page seeded by OCA on Thu Feb 21 14:22:03 2008
Categories: Homo sapiens | Protein complex | Liu, J. | Walker, N. | Wang, Z. | BR | IOD | K | Lbd | Nuur1
