1xj7
From Proteopedia
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'''Complex Androgen Receptor LBD and RAC3 peptide''' | '''Complex Androgen Receptor LBD and RAC3 peptide''' | ||
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[[Category: Nguyen, P.]] | [[Category: Nguyen, P.]] | ||
[[Category: Webb, P.]] | [[Category: Webb, P.]] | ||
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Revision as of 12:06, 3 May 2008
Complex Androgen Receptor LBD and RAC3 peptide
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
1XJ7 is a Single protein structure of sequence 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 Sat May 3 15:06:01 2008
