1zh7: Difference between revisions
New page: left|200px<br /><applet load="1zh7" size="450" color="white" frame="true" align="right" spinBox="true" caption="1zh7, resolution 2.50Å" /> '''Structural and Bioch... |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:1zh7.gif|left|200px]]<br /><applet load="1zh7" size=" | [[Image:1zh7.gif|left|200px]]<br /><applet load="1zh7" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1zh7, resolution 2.50Å" /> | caption="1zh7, resolution 2.50Å" /> | ||
'''Structural and Biochemical Basis for Selective Repression of the Orphan Nuclear Receptor LRH-1 by SHP'''<br /> | '''Structural and Biochemical Basis for Selective Repression of the Orphan Nuclear Receptor LRH-1 by SHP'''<br /> | ||
==Overview== | ==Overview== | ||
The functional interaction between the orphan nuclear receptors small | 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== | ==About this Structure== | ||
1ZH7 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http:// | 1ZH7 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZH7 OCA]. | ||
==Reference== | ==Reference== | ||
| Line 16: | Line 16: | ||
[[Category: Choi, M.]] | [[Category: Choi, M.]] | ||
[[Category: Daugherty, J.]] | [[Category: Daugherty, J.]] | ||
[[Category: Kliewer, S | [[Category: Kliewer, S A.]] | ||
[[Category: Kovach, A.]] | [[Category: Kovach, A.]] | ||
[[Category: Li, Y.]] | [[Category: Li, Y.]] | ||
[[Category: Suino, K.]] | [[Category: Suino, K.]] | ||
[[Category: Xu, H | [[Category: Xu, H E.]] | ||
[[Category: protein-peptide complex]] | [[Category: protein-peptide complex]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:15:30 2008'' | ||
Revision as of 17:15, 21 February 2008
|
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
Page seeded by OCA on Thu Feb 21 16:15:30 2008