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Interaction of the Androgen Receptor Ligand-Binding Domain with the N-Terminal Domain and with Coactivators

  • Jan Trapman
Chapter

Abstract

The ligand-binding domain of the androgen receptor not only binds ligands, but also contains a ligand-induced protein interaction surface, the cofactor-binding groove. The groove interacts with short amphipatic α-helices in cofactors composed of an FxxLF motif, or with LxxLL motifs at a lower affinity. Moreover, the cofactor-binding groove interacts with an FxxLF motif in the N-terminal domain of the androgen receptor. The groove is able to adapt its shape in complexes with interacting peptides. In the peptide motifs, an F at +1 seems essential for high-affinity binding. L+4 can be replaced by several other hydrophobic amino acid residues without losing activity. Although F at +5 has the highest activity, it can be substituted by tryptophane or tyrosine. Studies of the spatial and temporal distribution of the androgen receptor in the living cell indicates consecutive protein interactions, including intramolecular and intermolecular androgen receptor domain interactions and cofactor binding, depending on the cellular localization.

Keywords

Amino Acid Residue Androgen Receptor Cyproterone Acetate Peptide Motif Phenylalanine Residue 
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.

Notes

Acknowledgment

The author is indebted to Martin van Royen and Dennis van de Wijngaart for help with preparation of the manuscript.

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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Department of PathologyJosephine Nefkens Institute, Erasmus Medical CenterRotterdamThe Netherlands

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