View source for 1t5z

[[Image:1t5z.gif|left|200px]]<br /><applet load="1t5z" size="350" color="white" frame="true" align="right" spinBox="true" 
caption="1t5z, resolution 2.3&Aring;" />
'''Crystal Structure of the Androgen Receptor Ligand Binding Domain (LBD) with DHT and a peptide derived from its physiological coactivator ARA70'''<br />

==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:[[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]], Thyroid carcinoma, papillary OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=601984 601984]], Thyroid carcinoma, papillary OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=606918 606918]]

==About this Structure==
1T5Z 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=1T5Z 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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15563469 15563469]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Baxter, J D.]]
[[Category: Delgado-Rodrigues, E.]]
[[Category: Estebanez-Perpina, E.]]
[[Category: Fletterick, R J.]]
[[Category: Guy, R K.]]
[[Category: Mar, E.]]
[[Category: Moore, J M.R.]]
[[Category: Nguyen, P.]]
[[Category: Webb, P.]]
[[Category: DHT]]
[[Category: androgen receptor ligand binding domain ara70 crystal structure coactivators]]

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:10:12 2008''