1ovl
From Proteopedia
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|PDB= 1ovl |SIZE=350|CAPTION= <scene name='initialview01'>1ovl</scene>, resolution 2.2Å | |PDB= 1ovl |SIZE=350|CAPTION= <scene name='initialview01'>1ovl</scene>, resolution 2.2Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=BR:BROMIDE+ION'>BR</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= NR4A2 OR NURR1 OR TINUR OR NOT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= NR4A2 OR NURR1 OR TINUR OR NOT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ovl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ovl OCA], [http://www.ebi.ac.uk/pdbsum/1ovl PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1ovl RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==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. | 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:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=601828 601828]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Walker, N.]] | [[Category: Walker, N.]] | ||
[[Category: Wang, Z.]] | [[Category: Wang, Z.]] | ||
| - | [[Category: BR]] | ||
| - | [[Category: IOD]] | ||
| - | [[Category: K]] | ||
[[Category: lbd]] | [[Category: lbd]] | ||
[[Category: nuur1]] | [[Category: nuur1]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:50:57 2008'' |
Revision as of 19:50, 30 March 2008
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| , resolution 2.2Å | |||||||
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| Ligands: | , , , | ||||||
| Gene: | NR4A2 OR NURR1 OR TINUR OR NOT (Homo sapiens) | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal Structure of Nurr1 LBD
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.
About this Structure
1OVL is a Protein complex structure of sequences from Homo sapiens. 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 Sun Mar 30 22:50:57 2008
Categories: Homo sapiens | Protein complex | Liu, J. | Walker, N. | Wang, Z. | Lbd | Nuur1
