The Androgen Receptor Coactivator-Binding Interface



When hormone binds to the androgen receptor (AR), the ligand-binding domain (LBD) becomes ordered, displaying a new protein–protein interaction surface called AF2 (coactivator-binding pocket), which is a hydrophobic groove that fits AR coregulators. The association of coregulators with AR LBD is often a critical step for its transcriptional function. Existing pharmaceuticals block AR activity by disrupting AF2 surface's ability to recruit coactivators. Such antagonists bind to the hormone-binding site inside the LBD core and perturb the structure of the most terminal helix of the LBD, distorting the AF2 surface. The AF2 pocket is also a potential candidate for pharmaceutical intervention by surface-directed small molecules that will directly block coactivator recruitment. Such molecules may be a novel generation of antiandrogens for treating prostate cancer.


Androgen Receptor Phage Display Androgen Receptor Activity Hydrophobic Groove LXXLL Motif 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We thank Elena Sablin, Debra Singer, and Leslie Cruz for their useful comments on the manuscript.


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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Eva Estébanez-Perpiñá
  • Robert J. Fletterick
    • 1
  1. 1.Department of Biochemistry & Biophysics, University of California San FranciscoSan FranciscoUSA

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