1yuc: Difference between revisions
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|PDB= 1yuc |SIZE=350|CAPTION= <scene name='initialview01'>1yuc</scene>, resolution 1.90Å | |PDB= 1yuc |SIZE=350|CAPTION= <scene name='initialview01'>1yuc</scene>, resolution 1.90Å | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand=EPH:L-ALPHA-PHOSPHATIDYL-BETA-OLEOYL-GAMMA-PALMITOYL-PHOSPHATIDYLETHANOLAMINE'>EPH</scene> | |LIGAND= <scene name='pdbligand=EPH:L-ALPHA-PHOSPHATIDYL-BETA-OLEOYL-GAMMA-PALMITOYL-PHOSPHATIDYLETHANOLAMINE'>EPH</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene> | ||
|ACTIVITY= | |ACTIVITY= | ||
|GENE= NR5A2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= NR5A2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
|DOMAIN= | |||
|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> | |||
}} | }} | ||
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==Overview== | ==Overview== | ||
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. | 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 Structure== | ==About this Structure== | ||
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[[Category: Tripathy, A.]] | [[Category: Tripathy, A.]] | ||
[[Category: Yoonkwang, L.]] | [[Category: Yoonkwang, L.]] | ||
[[Category: | [[Category: liver receptor homologue 1]] | ||
[[Category: | [[Category: lrh-1]] | ||
[[Category: | [[Category: nuclear receptor ligand binding domain]] | ||
[[Category: phospholipid]] | |||
[[Category: shp]] | |||
[[Category: small heterodimer partner]] | |||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:22:43 2008'' | ||
