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4dor

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Revision as of 00:18, 5 August 2016

Human Nuclear Receptor Liver Receptor Homologue-1, LRH-1, in its apo State Bound to a Fragment of Human SHP Box1

Structural highlights

4dor is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	B1F, CPF, FTF, LRH-1, NR5A2 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[NR0B2_HUMAN] Defects in NR0B2 may be associated with obesity (OBESITY) [MIM:601665]. It is a condition characterized by an increase of body weight beyond the limitation of skeletal and physical requirements, as the result of excessive accumulation of body fat.^[1]

Function

[NR5A2_HUMAN] Binds to the sequence element 5'-AACGACCGACCTTGAG-3' of the enhancer II of hepatitis B virus genes, a critical cis-element of their expression and regulation. May be responsible for the liver-specific activity of enhancer II, probably in combination with other hepatocyte transcription factors. Key regulator of cholesterol 7-alpha-hydroxylase gene (CYP7A) expression in liver. May also contribute to the regulation of pancreas-specific genes and play important roles in embryonic development. [NR0B2_HUMAN] Acts as a transcriptional regulator. Acts as a negative regulator of receptor-dependent signaling pathways. Specifically inhibits transactivation of the nuclear receptor with whom it interacts. Inhibits transcriptional activity of NEUROD1 on E-box-containing promoter by interfering with the coactivation function of the p300/CBP-mediated trancription complex for NEUROD1.^[2]

Publication Abstract from PubMed

The human nuclear receptor liver receptor homolog-1 (LRH-1) has an important role in controlling lipid and cholesterol homeostasis and is a potential target for the treatment of diabetes and hepatic diseases. LRH-1 is known to bind phospholipids, but the role of phospholipids in controlling LRH-1 activation remains highly debated. Here we describe the structure of both apo LRH-1 and LRH-1 in complex with the antidiabetic phospholipid dilauroylphosphatidylcholine (DLPC). Together with hydrogen-deuterium exchange MS and functional data, our studies show that DLPC binding is a dynamic process that alters co-regulator selectivity. We show that the lipid-free receptor undergoes previously unrecognized structural fluctuations, allowing it to interact with widely expressed co-repressors. These observations enhance our understanding of LRH-1 regulation and highlight its importance as a new therapeutic target for controlling diabetes.

Antidiabetic phospholipid-nuclear receptor complex reveals the mechanism for phospholipid-driven gene regulation.,Musille PM, Pathak MC, Lauer JL, Hudson WH, Griffin PR, Ortlund EA Nat Struct Mol Biol. 2012 Apr 15;19(5):532-7. doi: 10.1038/nsmb.2279. PMID:22504882^[3]

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

References

↑ Nishigori H, Tomura H, Tonooka N, Kanamori M, Yamada S, Sho K, Inoue I, Kikuchi N, Onigata K, Kojima I, Kohama T, Yamagata K, Yang Q, Matsuzawa Y, Miki T, Seino S, Kim MY, Choi HS, Lee YK, Moore DD, Takeda J. Mutations in the small heterodimer partner gene are associated with mild obesity in Japanese subjects. Proc Natl Acad Sci U S A. 2001 Jan 16;98(2):575-80. Epub 2001 Jan 2. PMID:11136233 doi:10.1073/pnas.021544398
↑ Kim JY, Chu K, Kim HJ, Seong HA, Park KC, Sanyal S, Takeda J, Ha H, Shong M, Tsai MJ, Choi HS. Orphan nuclear receptor small heterodimer partner, a novel corepressor for a basic helix-loop-helix transcription factor BETA2/neuroD. Mol Endocrinol. 2004 Apr;18(4):776-90. Epub 2004 Jan 29. PMID:14752053 doi:10.1210/me.2003-0311
↑ Musille PM, Pathak MC, Lauer JL, Hudson WH, Griffin PR, Ortlund EA. Antidiabetic phospholipid-nuclear receptor complex reveals the mechanism for phospholipid-driven gene regulation. Nat Struct Mol Biol. 2012 Apr 15;19(5):532-7. doi: 10.1038/nsmb.2279. PMID:22504882 doi:10.1038/nsmb.2279

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4dor"

@@ Line 1: / Line 1: @@
 ==Human Nuclear Receptor Liver Receptor Homologue-1, LRH-1, in its apo State Bound to a Fragment of Human SHP Box1==
 <StructureSection load='4dor' size='340' side='right' caption='[[4dor]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4dor]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DOR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DOR FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4dor]] is a 4 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=4DOR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DOR FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EPH:L-ALPHA-PHOSPHATIDYL-BETA-OLEOYL-GAMMA-PALMITOYL-PHOSPHATIDYLETHANOLAMINE'>EPH</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">B1F, CPF, FTF, LRH-1, NR5A2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">B1F, CPF, FTF, LRH-1, NR5A2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4dor FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dor OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4dor RCSB], [http://www.ebi.ac.uk/pdbsum/4dor PDBsum]</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=4dor FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dor OCA], [http://pdbe.org/4dor PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4dor RCSB], [http://www.ebi.ac.uk/pdbsum/4dor PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4dor ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 19: / Line 20: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4dor" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Musille, P M]]
 [[Category: Ortlund, E A]]

4dor

From Proteopedia

Revision as of 00:18, 5 August 2016

Human Nuclear Receptor Liver Receptor Homologue-1, LRH-1, in its apo State Bound to a Fragment of Human SHP Box1

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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