5y41

From Proteopedia

(Difference between revisions)

Current revision

Crystal Structure of LIGAND-BOUND NURR1-LBD

Structural highlights

5y41 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.05Å
Ligands:	, , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

NR4A2_HUMAN Transcriptional regulator which is important for the differentiation and maintenance of meso-diencephalic dopaminergic (mdDA) neurons during development. It is crucial for expression of a set of genes such as SLC6A3, SLC18A2, TH and DRD2 which are essential for development of mdDA neurons (By similarity).

Publication Abstract from PubMed

The orphan nuclear receptor Nurr1 is critical for the development, maintenance and protection of midbrain dopaminergic (mDA) neurons. Here we show that prostaglandin E1 (PGE1) and its dehydrated metabolite, PGA1, directly interact with the ligand-binding domain (LBD) of Nurr1 and stimulate its transcriptional function. We also report the crystallographic structure of Nurr1-LBD bound to PGA1 at 2.05 A resolution. PGA1 couples covalently to Nurr1-LBD by forming a Michael adduct with Cys566, and induces notable conformational changes, including a 21 degrees shift of the activation function-2 helix (H12) away from the protein core. Furthermore, PGE1/PGA1 exhibit neuroprotective effects in a Nurr1-dependent manner, prominently enhance expression of Nurr1 target genes in mDA neurons and improve motor deficits in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mouse models of Parkinson's disease. Based on these results, we propose that PGE1/PGA1 represent native ligands of Nurr1 and can exert neuroprotective effects on mDA neurons, via activation of Nurr1's transcriptional function.

PGE1 and PGA1 bind to Nurr1 and activate its transcriptional function.,Rajan S, Jang Y, Kim CH, Kim W, Toh HT, Jeon J, Song B, Serra A, Lescar J, Yoo JY, Beldar S, Ye H, Kang C, Liu XW, Feitosa M, Kim Y, Hwang D, Goh G, Lim KL, Park HM, Lee CH, Oh SF, Petsko GA, Yoon HS, Kim KS Nat Chem Biol. 2020 May 25. pii: 10.1038/s41589-020-0553-6. doi:, 10.1038/s41589-020-0553-6. PMID:32451509^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Rajan S, Jang Y, Kim CH, Kim W, Toh HT, Jeon J, Song B, Serra A, Lescar J, Yoo JY, Beldar S, Ye H, Kang C, Liu XW, Feitosa M, Kim Y, Hwang D, Goh G, Lim KL, Park HM, Lee CH, Oh SF, Petsko GA, Yoon HS, Kim KS. PGE1 and PGA1 bind to Nurr1 and activate its transcriptional function. Nat Chem Biol. 2020 May 25. pii: 10.1038/s41589-020-0553-6. doi:, 10.1038/s41589-020-0553-6. PMID:32451509 doi:http://dx.doi.org/10.1038/s41589-020-0553-6

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5y41"

Categories: Homo sapiens | Large Structures | Lescar J | Sreekanth R | Yoon HS

@@ Line 3: / Line 3: @@
 <StructureSection load='5y41' size='340' side='right'caption='[[5y41]], [[Resolution|resolution]] 2.05&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5y41]] 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=5Y41 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5Y41 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5y41]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5Y41 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5Y41 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=RPG:(13E,15S)-15-hydroxy-9-oxoprosta-10,13-dien-1-oic+acid'>RPG</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.05&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NR4A2, NOT, NURR1, TINUR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=RPG:7-[(1~{R},5~{S})-2-oxidanylidene-5-[(~{E},3~{S})-3-oxidanyloct-1-enyl]cyclopent-3-en-1-yl]heptanoic+acid'>RPG</scene></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5y41 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5y41 OCA], [http://pdbe.org/5y41 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5y41 RCSB], [http://www.ebi.ac.uk/pdbsum/5y41 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5y41 ProSAT]</span></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=5y41 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5y41 OCA], [https://pdbe.org/5y41 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5y41 RCSB], [https://www.ebi.ac.uk/pdbsum/5y41 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5y41 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/NR4A2_HUMAN NR4A2_HUMAN]] Transcriptional regulator which is important for the differentiation and maintenance of meso-diencephalic dopaminergic (mdDA) neurons during development. It is crucial for expression of a set of genes such as SLC6A3, SLC18A2, TH and DRD2 which are essential for development of mdDA neurons (By similarity).
+[https://www.uniprot.org/uniprot/NR4A2_HUMAN NR4A2_HUMAN] Transcriptional regulator which is important for the differentiation and maintenance of meso-diencephalic dopaminergic (mdDA) neurons during development. It is crucial for expression of a set of genes such as SLC6A3, SLC18A2, TH and DRD2 which are essential for development of mdDA neurons (By similarity).
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 23: / Line 23: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Lescar, J]]
+[[Category: Lescar J]]
-[[Category: Sreekanth, R]]
+[[Category: Sreekanth R]]
-[[Category: Yoon, H S]]
+[[Category: Yoon HS]]
-[[Category: Lbd]]
-[[Category: Michael addition]]
-[[Category: Nurr1]]
-[[Category: Prostaglandin]]
-[[Category: Transcription]]

5y41

From Proteopedia

Current revision

Crystal Structure of LIGAND-BOUND NURR1-LBD

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox