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| | ==The crystal structure of the orphan nuclear receptor PNR ligand binding domain fused with MBP== | | ==The crystal structure of the orphan nuclear receptor PNR ligand binding domain fused with MBP== |
| - | <StructureSection load='4log' size='340' side='right' caption='[[4log]], [[Resolution|resolution]] 2.70Å' scene=''> | + | <StructureSection load='4log' size='340' side='right'caption='[[4log]], [[Resolution|resolution]] 2.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4log]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LOG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4LOG FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4log]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_O104:H4_str._2009EL-2071 Escherichia coli O104:H4 str. 2009EL-2071] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LOG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4LOG FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ECDH10B_4223, malE, O3O_01660, NR2E3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4log FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4log OCA], [https://pdbe.org/4log PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4log RCSB], [https://www.ebi.ac.uk/pdbsum/4log PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4log ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4log FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4log OCA], [http://pdbe.org/4log PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4log RCSB], [http://www.ebi.ac.uk/pdbsum/4log PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4log ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Disease == |
| | + | [https://www.uniprot.org/uniprot/NR2E3_HUMAN NR2E3_HUMAN] Goldmann-Favre syndrome;Retinitis pigmentosa. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/MALE_ECOLI MALE_ECOLI] Involved in the high-affinity maltose membrane transport system MalEFGK. Initial receptor for the active transport of and chemotaxis toward maltooligosaccharides.[https://www.uniprot.org/uniprot/NR2E3_HUMAN NR2E3_HUMAN] Orphan nuclear receptor of retinal photoreceptor cells. Transcriptional factor that is an activator of rod development and repressor of cone development. Binds the promoter region of a number of rod- and cone-specific genes, including rhodopsin, M- and S-opsin and rod-specific phosphodiesterase beta subunit. Enhances rhodopsin expression. Represses M- and S-cone opsin expression.<ref>PMID:15689355</ref> <ref>PMID:24069298</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 4log" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4log" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Maltose-binding protein 3D structures|Maltose-binding protein 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Escherichia coli O104:H4 str. 2009EL-2071]] |
| - | [[Category: Li, J]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Li, X]] | + | [[Category: Large Structures]] |
| - | [[Category: Melcher, K]] | + | [[Category: Li J]] |
| - | [[Category: Soon, F F]] | + | [[Category: Li X]] |
| - | [[Category: Tan, M E]] | + | [[Category: Melcher K]] |
| - | [[Category: Xu, H E]] | + | [[Category: Soon F-F]] |
| - | [[Category: Yong, E L]] | + | [[Category: Tan ME]] |
| - | [[Category: Zhou, X E]] | + | [[Category: Xu HE]] |
| - | [[Category: Ligand binding domain]]
| + | [[Category: Yong E-L]] |
| - | [[Category: Orphan nuclear receptor]]
| + | [[Category: Zhou XE]] |
| - | [[Category: Pnr]]
| + | |
| - | [[Category: Transcription]]
| + | |
| - | [[Category: Transcription factor]]
| + | |
| Structural highlights
Disease
NR2E3_HUMAN Goldmann-Favre syndrome;Retinitis pigmentosa. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry.
Function
MALE_ECOLI Involved in the high-affinity maltose membrane transport system MalEFGK. Initial receptor for the active transport of and chemotaxis toward maltooligosaccharides.NR2E3_HUMAN Orphan nuclear receptor of retinal photoreceptor cells. Transcriptional factor that is an activator of rod development and repressor of cone development. Binds the promoter region of a number of rod- and cone-specific genes, including rhodopsin, M- and S-opsin and rod-specific phosphodiesterase beta subunit. Enhances rhodopsin expression. Represses M- and S-cone opsin expression.[1] [2]
Publication Abstract from PubMed
Photoreceptor-specific nuclear receptor (PNR, NR2E3) is a key transcriptional regulator of human photoreceptor differentiation and maintenance. Mutations in the NR2E3-encoding gene cause various retinal degenerations, including Enhanced S-cone syndrome, retinitis pigmentosa, and Goldman-Favre disease. Although physiological ligands have not been identified, it is believed that binding of small molecule agonists, receptor desumoylation, and receptor heterodimerization may switch NR2E3 from a transcriptional repressor to an activator. While these features make NR2E3 a potential therapeutic target for the treatment of retinal diseases, there has been a clear lack of structural information for the receptor. Here, we report the crystal structure of the apo NR2E3 ligand binding domain (LBD) at 2.8 A resolution. Apo NR2E3 functions as transcriptional repressor in cells and the structure of its LBD is in a dimeric auto-repressed conformation. In this conformation, the putative ligand binding pocket is filled with bulky hydrophobic residues and the activation-function-2 (AF2) helix occupies the canonical cofactor binding site. Mutations designed to disrupt either the AF2/cofactor-binding site interface or the dimer interface compromised the transcriptional repressor activity of this receptor. Together, these results reveal several conserved structural features shared by related orphan nuclear receptors, suggest that most disease-causing mutations affect the receptor's structural integrity, and allowed us to model a putative active conformation that can accommodate small ligands in its pocket.
The Crystal Structure of the Orphan Nuclear Receptor NR2E3/PNR Ligand Binding Domain Reveals a Dimeric Auto-Repressed Conformation.,Tan MH, Zhou XE, Soon FF, Li X, Li J, Yong EL, Melcher K, Xu HE PLoS One. 2013 Sep 12;8(9):e74359. doi: 10.1371/journal.pone.0074359. PMID:24069298[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Peng GH, Ahmad O, Ahmad F, Liu J, Chen S. The photoreceptor-specific nuclear receptor Nr2e3 interacts with Crx and exerts opposing effects on the transcription of rod versus cone genes. Hum Mol Genet. 2005 Mar 15;14(6):747-64. doi: 10.1093/hmg/ddi070. Epub 2005 Feb , 2. PMID:15689355 doi:http://dx.doi.org/10.1093/hmg/ddi070
- ↑ Tan MH, Zhou XE, Soon FF, Li X, Li J, Yong EL, Melcher K, Xu HE. The Crystal Structure of the Orphan Nuclear Receptor NR2E3/PNR Ligand Binding Domain Reveals a Dimeric Auto-Repressed Conformation. PLoS One. 2013 Sep 12;8(9):e74359. doi: 10.1371/journal.pone.0074359. PMID:24069298 doi:http://dx.doi.org/10.1371/journal.pone.0074359
- ↑ Tan MH, Zhou XE, Soon FF, Li X, Li J, Yong EL, Melcher K, Xu HE. The Crystal Structure of the Orphan Nuclear Receptor NR2E3/PNR Ligand Binding Domain Reveals a Dimeric Auto-Repressed Conformation. PLoS One. 2013 Sep 12;8(9):e74359. doi: 10.1371/journal.pone.0074359. PMID:24069298 doi:http://dx.doi.org/10.1371/journal.pone.0074359
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