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.
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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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Trapman, J. (2009). Interaction of the Androgen Receptor Ligand-Binding Domain with the N-Terminal Domain and with Coactivators. In: Mohler, J., Tindall, D. (eds) Androgen Action in Prostate Cancer. Springer, New York, NY. https://doi.org/10.1007/978-0-387-69179-4_16
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DOI: https://doi.org/10.1007/978-0-387-69179-4_16
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