1T65

Crystal structure of the androgen receptor ligand binding domain with DHT and a peptide derived form its physiological coactivator GRIP1 NR box 2 bound in a non-helical conformation

Summary for 1T65

• Entry DOI: 10.2210/pdb1t65/pdb
• Related: 1T5Z 1T63
• Descriptor: Androgen receptor, Nuclear receptor coactivator 2, 5-ALPHA-DIHYDROTESTOSTERONE, ... (4 entities in total)
• Functional Keywords: androgen receptor ligand binding domain grip1 nr box2 coactivators crystal structure non-helical, hormone-growth factor complex, hormone/growth factor
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus : P10275 Q15596
• Total number of polymer chains: 2
• Total formula weight: 31147.65

Authors

Estebanez-Perpina, E.,Moore, J.M.R.,Mar, E.,Nguyen, P.,Delgado-Rodrigues, E.,Baxter, J.D.,Webb, P.,Fletterick, R.J.,Guy, R.K. (deposition date: 2004-05-05, release date: 2005-01-25, Last modification date: 2024-02-14)

Primary citation

Estebanez-Perpina, E.,Moore, J.M.R.,Mar, E.,Delgado-Rodrigues, E.,Nguyen, P.,Baxter, J.D.,Buehrer, B.M.,Webb, P.,Fletterick, R.J.,Guy, R.K.
The Molecular Mechanisms of Coactivator Utilization in Ligand-dependent Transactivation by the Androgen Receptor.
J.Biol.Chem., 280:8060-8068, 2005

PubMed Abstract: 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.

PubMed: 15563469
DOI: 10.1074/jbc.M407046200

Experimental method

X-RAY DIFFRACTION (1.66 Å)