1zh7
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Structural and Biochemical Basis for Selective Repression of the Orphan Nuclear Receptor LRH-1 by SHP
OverviewOverview
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 StructureAbout this Structure
1ZH7 is a Protein complex structure of sequences from Mus musculus and Rattus norvegicus. Full crystallographic information is available from OCA.
ReferenceReference
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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