1zh7
From Proteopedia
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|GENE= | |GENE= | ||
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| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1zh7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zh7 OCA], [http://www.ebi.ac.uk/pdbsum/1zh7 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1zh7 RCSB]</span> | ||
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[[Category: protein-peptide complex]] | [[Category: protein-peptide complex]] | ||
| - | ''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 01:36:32 2008'' |
Revision as of 22:36, 30 March 2008
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| , resolution 2.50Å | |||||||
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Structural and Biochemical Basis for Selective Repression of the Orphan Nuclear Receptor LRH-1 by SHP
Overview
The functional interaction between the orphan nuclear receptors small heterodimer partner (SHP) and liver receptor homolog 1 (LRH-1), where SHP binds to LRH-1 and represses its constitutive transcriptional activity, is crucial for regulating genes involved in cholesterol homeostasis. Here, we report structural and biochemical analyses of the LRH-1/SHP interaction. The crystal structure and modeling studies of the LRH-1 ligand-binding domain bound to either of the two LXXLL-related motifs of SHP show that the receptor undergoes conformational changes to accommodate the SHP docking and reveal key residues that determine the potency and selectivity of SHP binding. Through a combination of mutagenesis and binding studies, we demonstrate that only the second SHP LXXLL motif is required for repressing LRH-1, and this motif displays a strong preference for binding to LRH-1 over the closely related receptor steroidogeneic factor 1 (SF-1). Structural comparisons indicate that this binding selectivity is determined by residues flanking the core LXXLL motifs. These results establish a structural model for understanding how SHP interacts with LRH-1 to regulate cholesterol homeostasis and provide new insights into how nuclear receptor/coregulator selectivity is achieved.
About this Structure
1ZH7 is a Protein complex structure of sequences from Mus musculus and Rattus norvegicus. Full crystallographic information is available from OCA.
Reference
Structural and biochemical basis for selective repression of the orphan nuclear receptor liver receptor homolog 1 by small heterodimer partner., Li Y, Choi M, Suino K, Kovach A, Daugherty J, Kliewer SA, Xu HE, Proc Natl Acad Sci U S A. 2005 Jul 5;102(27):9505-10. Epub 2005 Jun 23. PMID:15976031
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