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6kz5

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Crystal Structure Analysis of the Csn-B-bounded NUR77 Ligand binding Domain

Structural highlights

6kz5 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 4.45Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

NR4A1_HUMAN Orphan nuclear receptor. May act concomitantly with NURR1 in regulating the expression of delayed-early genes during liver regeneration. Binds the NGFI-B response element (NBRE) 5'-AAAAGGTCA-3' (By similarity). May inhibit NF-kappa-B transactivation of IL2.^[1]

Publication Abstract from PubMed

Nuclear receptor Nur77 participates in multiple metabolic regulations and plays paradoxical roles in tumorigeneses. Herein, we demonstrated that the knockout of Nur77 stimulated mammary tumor development in two mouse models, which would be reversed by a specific reexpression of Nur77 in mammary tissues. Mechanistically, Nur77 interacted and recruited corepressors, the SWI/SNF complex, to the promoters of CD36 and FABP4 to suppress their transcriptions, which hampered the fatty acid uptake, leading to the inhibition of cell proliferation. Peroxisome proliferator-activated receptor-gamma (PPARgamma) played an antagonistic role in this process through binding to Nur77 to facilitate ubiquitin ligase Trim13-mediated ubiquitination and degradation of Nur77. Cocrystallographic and functional analysis revealed that Csn-B, a Nur77-targeting compound, promoted the formation of Nur77 homodimer to prevent PPARgamma binding by steric hindrance, thereby strengthening the Nur77's inhibitory role in breast cancer. Therefore, our study reveals a regulatory function of Nur77 in breast cancer via impeding fatty acid uptake.

Blocking PPARgamma interaction facilitates Nur77 interdiction of fatty acid uptake and suppresses breast cancer progression.,Yang PB, Hou PP, Liu FY, Hong WB, Chen HZ, Sun XY, Li P, Zhang Y, Ju CY, Luo LJ, Wu SF, Zhou JX, Wang ZJ, He JP, Li L, Zhao TJ, Deng X, Lin T, Wu Q Proc Natl Acad Sci U S A. 2020 Oct 21. pii: 2002997117. doi:, 10.1073/pnas.2002997117. PMID:33087562^[2]

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

References

↑ Harant H, Lindley IJ. Negative cross-talk between the human orphan nuclear receptor Nur77/NAK-1/TR3 and nuclear factor-kappaB. Nucleic Acids Res. 2004 Oct 5;32(17):5280-90. Print 2004. PMID:15466594 doi:10.1093/nar/gkh856
↑ Yang PB, Hou PP, Liu FY, Hong WB, Chen HZ, Sun XY, Li P, Zhang Y, Ju CY, Luo LJ, Wu SF, Zhou JX, Wang ZJ, He JP, Li L, Zhao TJ, Deng X, Lin T, Wu Q. Blocking PPARgamma interaction facilitates Nur77 interdiction of fatty acid uptake and suppresses breast cancer progression. Proc Natl Acad Sci U S A. 2020 Oct 21. pii: 2002997117. doi:, 10.1073/pnas.2002997117. PMID:33087562 doi:http://dx.doi.org/10.1073/pnas.2002997117

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/6kz5"

@@ Line 3: / Line 3: @@
 <StructureSection load='6kz5' size='340' side='right'caption='[[6kz5]], [[Resolution|resolution]] 4.45&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6kz5]] 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=6KZ5 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6KZ5 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6kz5]] 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=6KZ5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6KZ5 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=E4L:ethyl+2-[2-octanoyl-3,5-bis(oxidanyl)phenyl]ethanoate'>E4L</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]] 4.45&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NR4A1, GFRP1, HMR, NAK1 ([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=E4L:ethyl+2-[2-octanoyl-3,5-bis(oxidanyl)phenyl]ethanoate'>E4L</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=6kz5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kz5 OCA], [http://pdbe.org/6kz5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6kz5 RCSB], [http://www.ebi.ac.uk/pdbsum/6kz5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6kz5 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=6kz5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kz5 OCA], [https://pdbe.org/6kz5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6kz5 RCSB], [https://www.ebi.ac.uk/pdbsum/6kz5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6kz5 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/NR4A1_HUMAN NR4A1_HUMAN]] Orphan nuclear receptor. May act concomitantly with NURR1 in regulating the expression of delayed-early genes during liver regeneration. Binds the NGFI-B response element (NBRE) 5'-AAAAGGTCA-3' (By similarity). May inhibit NF-kappa-B transactivation of IL2.<ref>PMID:15466594</ref>
+[https://www.uniprot.org/uniprot/NR4A1_HUMAN NR4A1_HUMAN] Orphan nuclear receptor. May act concomitantly with NURR1 in regulating the expression of delayed-early genes during liver regeneration. Binds the NGFI-B response element (NBRE) 5'-AAAAGGTCA-3' (By similarity). May inhibit NF-kappa-B transactivation of IL2.<ref>PMID:15466594</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 23: / Line 23: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Chen, H]]
+[[Category: Chen H]]
-[[Category: Hong, W]]
+[[Category: Hong W]]
-[[Category: Lin, T]]
+[[Category: Lin T]]
-[[Category: Wu, Q]]
+[[Category: Wu Q]]
-[[Category: Nr4a1]]
-[[Category: Nur77]]
-[[Category: Transcription]]

6kz5

From Proteopedia

Current revision

Crystal Structure Analysis of the Csn-B-bounded NUR77 Ligand binding Domain

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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