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1yuc

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[[Image:1yuc.gif|left|200px]]
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{{STRUCTURE_1yuc| PDB=1yuc | SCENE= }}
{{STRUCTURE_1yuc| PDB=1yuc | SCENE= }}
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'''Human Nuclear Receptor Liver Receptor Homologue-1, LRH-1, Bound to Phospholipid and a Fragment of Human SHP'''
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===Human Nuclear Receptor Liver Receptor Homologue-1, LRH-1, Bound to Phospholipid and a Fragment of Human SHP===
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==Overview==
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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.
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The line below this paragraph, {{ABSTRACT_PUBMED_15723037}}, adds the Publication Abstract to the page
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(as it appears on PubMed at http://www.pubmed.gov), where 15723037 is the PubMed ID number.
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{{ABSTRACT_PUBMED_15723037}}
==About this Structure==
==About this Structure==
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[[Category: Shp]]
[[Category: Shp]]
[[Category: Small heterodimer partner]]
[[Category: Small heterodimer partner]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 16:47:56 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 20:46:38 2008''

Revision as of 17:46, 27 July 2008

Image:1yuc.png

Template:STRUCTURE 1yuc

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

Template:ABSTRACT PUBMED 15723037

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 Sun Jul 27 20:46:38 2008

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