1yuc: Difference between revisions

Revision as of 16:47, 3 May 2008

Human Nuclear Receptor Liver Receptor Homologue-1, LRH-1, Bound to Phospholipid and a Fragment of Human SHP

OverviewOverview

The human nuclear receptor liver receptor homolog 1 (hLRH-1) plays an important role in the development of breast carcinomas. This orphan receptor is efficiently downregulated by the unusual co-repressor SHP and has been thought to be ligand-independent. We present the crystal structure at a resolution of 1.9 A of the ligand-binding domain of hLRH-1 in complex with the NR box 1 motif of human SHP, which we find contacts the AF-2 region of hLRH-1 using selective structural motifs. Electron density indicates phospholipid bound within the ligand-binding pocket, which we confirm using mass spectrometry of solvent-extracted samples. We further show that pocket mutations reduce phospholipid binding and receptor activity in vivo. Our results indicate that hLRH-1's control of gene expression is mediated by phospholipid binding, and establish hLRH-1 as a novel target for compounds designed to slow breast cancer development.

About this StructureAbout this Structure

1YUC is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

Modulation of human nuclear receptor LRH-1 activity by phospholipids and SHP., Ortlund EA, Lee Y, Solomon IH, Hager JM, Safi R, Choi Y, Guan Z, Tripathy A, Raetz CR, McDonnell DP, Moore DD, Redinbo MR, Nat Struct Mol Biol. 2005 Apr;12(4):357-63. Epub 2005 Feb 22. PMID:15723037 Page seeded by OCA on Sat May 3 16:47:56 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
 [[Image:1yuc.gif|left|200px]]
- {{Structure
+<!--
-|PDB= 1yuc |SIZE=350|CAPTION= <scene name='initialview01'>1yuc</scene>, resolution 1.90&Aring;
+The line below this paragraph, containing "STRUCTURE_1yuc", creates the "Structure Box" on the page.
-|SITE=
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=EPH:L-ALPHA-PHOSPHATIDYL-BETA-OLEOYL-GAMMA-PALMITOYL-PHOSPHATIDYLETHANOLAMINE'>EPH</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY=
+or leave the SCENE parameter empty for the default display.
-|GENE= NR5A2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
+-->
-|DOMAIN=
+{{STRUCTURE_1yuc|  PDB=1yuc  |  SCENE=  }}
-|RELATEDENTRY=
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1yuc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1yuc OCA], [http://www.ebi.ac.uk/pdbsum/1yuc PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1yuc RCSB]</span>
-}}
 '''Human Nuclear Receptor Liver Receptor Homologue-1, LRH-1, Bound to Phospholipid and a Fragment of Human SHP'''
@@ Line 37: / Line 34: @@
 [[Category: Tripathy, A.]]
 [[Category: Yoonkwang, L.]]
-[[Category: liver receptor homologue 1]]
+[[Category: Liver receptor homologue 1]]
-[[Category: lrh-1]]
+[[Category: Lrh-1]]
-[[Category: nuclear receptor ligand binding domain]]
+[[Category: Nuclear receptor ligand binding domain]]
-[[Category: phospholipid]]
+[[Category: Phospholipid]]
-[[Category: shp]]
+[[Category: Shp]]
-[[Category: small heterodimer partner]]
+[[Category: Small heterodimer partner]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 16:47:56 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:22:43 2008''