1t63
From Proteopedia
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|ACTIVITY= | |ACTIVITY= | ||
|GENE= AR, NR3C4, DHTR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), NCOA2, TIF2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= AR, NR3C4, DHTR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), NCOA2, TIF2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1t5z|1T5Z]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1t63 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t63 OCA], [http://www.ebi.ac.uk/pdbsum/1t63 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1t63 RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==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. | 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. | ||
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| - | ==Disease== | ||
| - | Known diseases associated with this structure: Androgen insensitivity OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=313700 313700]], Breast cancer, male, with Reifenstein syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=313700 313700]], Hypospadias, perineal OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=313700 313700]], Prostate cancer OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=313700 313700]], Prostate cancer, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=313700 313700]], Spinal and bulbar muscular atrophy of Kennedy OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=313700 313700]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Nguyen, P.]] | [[Category: Nguyen, P.]] | ||
[[Category: Webb, P.]] | [[Category: Webb, P.]] | ||
| - | [[Category: DHT]] | ||
[[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://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 23:51:48 2008'' |
Revision as of 20:51, 30 March 2008
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| , resolution 2.07Å | |||||||
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| Ligands: | |||||||
| Gene: | AR, NR3C4, DHTR (Homo sapiens), NCOA2, TIF2 (Homo sapiens) | ||||||
| Related: | 1T5Z
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal Structure of the Androgen Receptor Ligand Binding Domain with DHT and a peptide derived from its physiological coactivator GRIP1 NR box3
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.
About this Structure
1T63 is a Protein complex structure of sequences from Homo sapiens. 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
Page seeded by OCA on Sun Mar 30 23:51:48 2008
