1yuc
From Proteopedia
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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. | ||
| - | |||
| - | ==Disease== | ||
| - | Known diseases associated with this structure: Obesity, mild, early-onset OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=604630 604630]] | ||
==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'' |
Revision as of 22:22, 30 March 2008
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| , resolution 1.90Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Gene: | NR5A2 (Homo sapiens) | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Human Nuclear Receptor Liver Receptor Homologue-1, LRH-1, Bound to Phospholipid and a Fragment of Human SHP
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.
About this Structure
1YUC is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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 Mon Mar 31 01:22:43 2008
Categories: Homo sapiens | Protein complex | Choi, Y. | Guan, Z. | Hager, J M. | McDonnell, D P. | Moore, D D. | Ortlund, E A. | Raetz, C R.H. | Redinbo, M R. | Safi, R. | Solomon, I H. | Tripathy, A. | Yoonkwang, L. | Liver receptor homologue 1 | Lrh-1 | Nuclear receptor ligand binding domain | Phospholipid | Shp | Small heterodimer partner
