1xj7
From Proteopedia
(New page: 200px<br /> <applet load="1xj7" size="450" color="white" frame="true" align="right" spinBox="true" caption="1xj7, resolution 2.7Å" /> '''Complex Androgen Rec...) |
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| - | [[Image:1xj7.gif|left|200px]]<br /> | + | [[Image:1xj7.gif|left|200px]]<br /><applet load="1xj7" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1xj7" size=" | + | |
caption="1xj7, resolution 2.7Å" /> | caption="1xj7, resolution 2.7Å" /> | ||
'''Complex Androgen Receptor LBD and RAC3 peptide'''<br /> | '''Complex Androgen Receptor LBD and RAC3 peptide'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Androgens drive sex differentiation, bone and muscle development, and | + | Androgens drive sex differentiation, bone and muscle development, and promote growth of hormone-dependent cancers by binding the nuclear androgen receptor (AR), which recruits coactivators to responsive genes. Most nuclear receptors recruit steroid receptor coactivators (SRCs) to their ligand binding domain (LBD) using a leucine-rich motif (LXXLL). AR is believed to recruit unique coactivators to its LBD using an aromatic-rich motif (FXXLF) while recruiting SRCs to its N-terminal domain (NTD) through an alternate mechanism. Here, we report that the AR-LBD interacts with both FXXLF motifs and a subset of LXXLL motifs and that contacts with these LXXLL motifs are both necessary and sufficient for SRC-mediated AR regulation of transcription. Crystal structures of the activated AR in complex with both recruitment motifs reveal that side chains unique to the AR-LBD rearrange to bind either the bulky FXXLF motifs or the more compact LXXLL motifs and that AR utilizes subsidiary contacts with LXXLL flanking sequences to discriminate between LXXLL motifs. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1XJ7 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with DHT as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1XJ7 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=DHT:'>DHT</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XJ7 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Baxter, J | + | [[Category: Baxter, J D.]] |
| - | [[Category: Buehrer, B | + | [[Category: Buehrer, B M.]] |
[[Category: Delgado-Rodrigues, E.]] | [[Category: Delgado-Rodrigues, E.]] | ||
[[Category: Estebanez-Perpina, E.]] | [[Category: Estebanez-Perpina, E.]] | ||
| - | [[Category: Fletterick, R | + | [[Category: Fletterick, R J.]] |
| - | [[Category: Guy, R | + | [[Category: Guy, R K.]] |
[[Category: Mar, E.]] | [[Category: Mar, E.]] | ||
| - | [[Category: Moore, J | + | [[Category: Moore, J M.R.]] |
[[Category: Nguyen, P.]] | [[Category: Nguyen, P.]] | ||
[[Category: Webb, P.]] | [[Category: Webb, P.]] | ||
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[[Category: androgen receptor coactivators lxxll motif]] | [[Category: androgen receptor coactivators lxxll motif]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:55:22 2008'' |
Revision as of 13:55, 21 February 2008
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Complex Androgen Receptor LBD and RAC3 peptide
Contents |
Overview
Androgens drive sex differentiation, bone and muscle development, and promote growth of hormone-dependent cancers by binding the nuclear androgen receptor (AR), which recruits coactivators to responsive genes. Most nuclear receptors recruit steroid receptor coactivators (SRCs) to their ligand binding domain (LBD) using a leucine-rich motif (LXXLL). AR is believed to recruit unique coactivators to its LBD using an aromatic-rich motif (FXXLF) while recruiting SRCs to its N-terminal domain (NTD) through an alternate mechanism. Here, we report that the AR-LBD interacts with both FXXLF motifs and a subset of LXXLL motifs and that contacts with these LXXLL motifs are both necessary and sufficient for SRC-mediated AR regulation of transcription. Crystal structures of the activated AR in complex with both recruitment motifs reveal that side chains unique to the AR-LBD rearrange to bind either the bulky FXXLF motifs or the more compact LXXLL motifs and that AR utilizes subsidiary contacts with LXXLL flanking sequences to discriminate between LXXLL motifs.
Disease
Known diseases associated with this structure: Androgen insensitivity OMIM:[313700], Breast cancer, male, with Reifenstein syndrome OMIM:[313700], Hypospadias, perineal OMIM:[313700], Prostate cancer OMIM:[313700], Prostate cancer, susceptibility to OMIM:[313700], Spinal and bulbar muscular atrophy of Kennedy OMIM:[313700]
About this Structure
1XJ7 is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
Reference
The molecular mechanisms of coactivator utilization in ligand-dependent transactivation by the androgen receptor., Estebanez-Perpina E, Moore JM, Mar E, Delgado-Rodrigues E, Nguyen P, Baxter JD, Buehrer BM, Webb P, Fletterick RJ, Guy RK, J Biol Chem. 2005 Mar 4;280(9):8060-8. Epub 2004 Nov 24. PMID:15563469
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