2z4j: Difference between revisions

Revision as of 20:00, 21 February 2008

Crystal structure of AR LBD with SHP peptide NR Box 2

OverviewOverview

The mechanisms of functional repression of the androgen receptor (AR) are crucial for the regulation of genes involved in physiological development as well as for the progression of prostate cancer. To date, only two in vivo inhibitors of AR-mediated transcription have been identified: DAX-1 and SHP (small heterodimer partner). SHP is a regulatory nuclear receptor (NR) that lacks DNA-binding and activation domains. Using X-ray crystallography, the interaction between peptide segments of the SHP repressor containing LxxLL-like motifs and the ligand-binding domain of AR have been investigated. Under the crystallization conditions used, it was found that of the three NR Boxes present in the SHP protein sequence, only NR Box 2 (LKKIL motif) formed a complex with AR. Determination of the crystal structure revealed that ten amino acids of the SHP peptide (14-mer) are ordered through interactions with AR. Two side chains make unique interactions that were not reported for other AR-peptide complexes. The NR Box 2 of SHP binds to an adaptable hydrophobic groove on the surface of AR in a fashion observed for other NR-LxxLL-like complexes. Comparisons of AR structures bound to coactivator peptides and the SHP peptide revealed structural similarity of their binding sites, suggesting that transcriptional AR activity may be inhibited by SHP by competing with AR coactivators.

About this StructureAbout this Structure

2Z4J is a Protein complex structure of sequences from Homo sapiens with as ligand. Full crystallographic information is available from OCA.

ReferenceReference

Interaction between the androgen receptor and a segment of its corepressor SHP., Jouravel N, Sablin E, Arnold LA, Guy RK, Fletterick RJ, Acta Crystallogr D Biol Crystallogr. 2007 Nov;63(Pt 11):1198-200. Epub, 2007 Oct 17. PMID:18007036

Page seeded by OCA on Thu Feb 21 19:00:08 2008

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OCA

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 ==Overview==
-The mechanisms of functional repression of the androgen receptor (AR) are, crucial for the regulation of genes involved in physiological development, as well as for the progression of prostate cancer. To date, only two in, vivo inhibitors of AR-mediated transcription have been identified: DAX-1, and SHP (small heterodimer partner). SHP is a regulatory nuclear receptor, (NR) that lacks DNA-binding and activation domains. Using X-ray, crystallography, the interaction between peptide segments of the SHP, repressor containing LxxLL-like motifs and the ligand-binding domain of AR, have been investigated. Under the crystallization conditions used, it was, found that of the three NR Boxes present in the SHP protein sequence, only, NR Box 2 (LKKIL motif) formed a complex with AR. Determination of the, crystal structure revealed that ten amino acids of the SHP peptide, (14-mer) are ordered through interactions with AR. Two side chains make, unique interactions that were not reported for other AR-peptide complexes., The NR Box 2 of SHP binds to an adaptable hydrophobic groove on the, surface of AR in a fashion observed for other NR-LxxLL-like complexes., Comparisons of AR structures bound to coactivator peptides and the SHP, peptide revealed structural similarity of their binding sites, suggesting, that transcriptional AR activity may be inhibited by SHP by competing with, AR coactivators.
+The mechanisms of functional repression of the androgen receptor (AR) are crucial for the regulation of genes involved in physiological development as well as for the progression of prostate cancer. To date, only two in vivo inhibitors of AR-mediated transcription have been identified: DAX-1 and SHP (small heterodimer partner). SHP is a regulatory nuclear receptor (NR) that lacks DNA-binding and activation domains. Using X-ray crystallography, the interaction between peptide segments of the SHP repressor containing LxxLL-like motifs and the ligand-binding domain of AR have been investigated. Under the crystallization conditions used, it was found that of the three NR Boxes present in the SHP protein sequence, only NR Box 2 (LKKIL motif) formed a complex with AR. Determination of the crystal structure revealed that ten amino acids of the SHP peptide (14-mer) are ordered through interactions with AR. Two side chains make unique interactions that were not reported for other AR-peptide complexes. The NR Box 2 of SHP binds to an adaptable hydrophobic groove on the surface of AR in a fashion observed for other NR-LxxLL-like complexes. Comparisons of AR structures bound to coactivator peptides and the SHP peptide revealed structural similarity of their binding sites, suggesting that transcriptional AR activity may be inhibited by SHP by competing with AR coactivators.
 ==About this Structure==
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 [[Category: Homo sapiens]]
 [[Category: Protein complex]]
-[[Category: Fletterick, R.J.]]
+[[Category: Fletterick, R J.]]
 [[Category: Jouravel, N.]]
 [[Category: DHT]]
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 [[Category: transcription]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 11:54:02 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 19:00:08 2008''