1t63
From Proteopedia
(New page: 200px<br /> <applet load="1t63" size="450" color="white" frame="true" align="right" spinBox="true" caption="1t63, resolution 2.07Å" /> '''Crystal Structure o...) |
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| - | [[Image:1t63.gif|left|200px]]<br /> | + | [[Image:1t63.gif|left|200px]]<br /><applet load="1t63" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1t63" size=" | + | |
caption="1t63, resolution 2.07Å" /> | caption="1t63, resolution 2.07Å" /> | ||
'''Crystal Structure of the Androgen Receptor Ligand Binding Domain with DHT and a peptide derived from its physiological coactivator GRIP1 NR box3'''<br /> | '''Crystal Structure of the Androgen Receptor Ligand Binding Domain with DHT and a peptide derived from its physiological coactivator GRIP1 NR box3'''<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== | ||
| - | 1T63 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences 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:// | + | 1T63 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences 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=1T63 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Baxter, J | + | [[Category: Baxter, J D.]] |
[[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 ligand binding domain grip1 nr boxes coactivators dht crystal structure]] | [[Category: androgen receptor ligand binding domain grip1 nr boxes coactivators dht crystal structure]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:10:13 2008'' |
Revision as of 13:10, 21 February 2008
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Crystal Structure of the Androgen Receptor Ligand Binding Domain with DHT and a peptide derived from its physiological coactivator GRIP1 NR box3
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
1T63 is a Protein complex structure of sequences 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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