3L3X

Crystal structure of DHT-bound androgen receptor in complex with the first motif of steroid receptor coactivator 3

Summary for 3L3X

• Entry DOI: 10.2210/pdb3l3x/pdb
• Related: 3L3Z
• Descriptor: Androgen receptor, Nuclear receptor coactivator 3, 5-ALPHA-DIHYDROTESTOSTERONE, ... (4 entities in total)
• Functional Keywords: androgen receptor, ligand binding domain, steroid receptor coactivator 3, 5-alpha-dihydrotestosterone (dht), prostate cancer, protein binding
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus : P10275; Cytoplasm: Q9Y6Q9
• Total number of polymer chains: 2
• Total formula weight: 30797.27

Authors

Zhou, X.E.,Suino-Powell, K.M.,Li, J.,He, A.,MacKeigan, J.P.,Melcher, K.,Yong, E.-L.,Xu, H.E. (deposition date: 2009-12-18, release date: 2010-01-12, Last modification date: 2024-10-16)

Primary citation

Zhou, X.E.,Suino-Powell, K.M.,Li, J.,He, Y.,Mackeigan, J.P.,Melcher, K.,Yong, E.L.,Xu, H.E.
Identification of SRC3/AIB1 as a Preferred Coactivator for Hormone-activated Androgen Receptor.
J.Biol.Chem., 285:9161-9171, 2010

PubMed Abstract: Transcription activation by androgen receptor (AR), which depends on recruitment of coactivators, is required for the initiation and progression of prostate cancer, yet the mechanisms of how hormone-activated AR interacts with coactivators remain unclear. This is because AR, unlike any other nuclear receptor, prefers its own N-terminal FXXLF motif to the canonical LXXLL motifs of coactivators. Through biochemical and crystallographic studies, we identify that steroid receptor coactivator-3 (SRC3) (also named as amplified in breast cancer-1 or AIB1) interacts strongly with AR via synergistic binding of its first and third LXXLL motifs. Mutagenesis and functional studies confirm that SRC3 is a preferred coactivator for hormone-activated AR. Importantly, AR mutations found in prostate cancer patients correlate with their binding potency to SRC3, corroborating with the emerging role of SRC3 as a prostate cancer oncogene. These results provide a molecular mechanism for the selective utilization of SRC3 by hormone-activated AR, and they link the functional relationship between AR and SRC3 to the development and growth of prostate cancer.

PubMed: 20086010
DOI: 10.1074/jbc.M109.085779

Experimental method

X-RAY DIFFRACTION (1.55 Å)