Sandbox GGC9

Androgen receptor

spinqualitylabelsall models androgen receptor Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D This is a default text for your page Sandbox GGC9. Click above on edit this page to modify. Be careful with the < and > signs. You may include any references to papers as in: the use of JSmol in Proteopedia or to the article describing Jmol to the rescue. Background The androgen receptor (AR) is a member of the nuclear receptor superfamily of ligand-activated transcription factors. Androgen activation of AR regulates prostate growth, bone, muscle mass, and spermatogenesis. A ligand, usually testosterone, binds to the receptor and causes a conformational change to cause down stream effects. ligands The ligands that have a high affinity to the AR are Testosterone (T) and Dihydrotestosterone (DHT). Testosterone is a cholesterol derivative, this hormone helps facilitate male maturation and development. Dihydrotestosterone is a tissue metabolite of testosterone and is significantly more potent then testosterone. Testosterone Ball and stick binding pocket The way AR binds the dozens of coregulator proteins reported to associate with different regions of AR are poorly understood. Nuclear receptors activate transcription by binding short sequences such as LxxLL or FXXLF (where “x” is any amino acid). these residues bid to the OH group on the testosterone and allow for pocket stabilization.Androgen receptor binding pocket W/O ligand Relevance the AR binds to testosterone to induce masculinization of males during the age of puberty. this allows for the development of male characteristics such as facial hair, deepening of the voice, sperm production and overall build. depending on the residue in the LXXLL motifs, the ligand binding may change. A FXXLF sequence mutation and a second N-terminal WXXLF sequence interact with different regions of the ligand binding site to stabilize the AR complex and may compete with AF2 recruitment of LXXLL motif-containing coactivators. The results suggest a unique mechanism for AR-mediated transcriptional activation. Structural highlights androgen recepto With ligand This is a sample scene created with SAT to color by Group, and another to make a transparent representation of the protein.

References

1. Askew EB, Gampe RT Jr, Stanley TB, Faggart JL, Wilson EM. Modulation of androgen receptor activation function 2 by testosterone and dihydrotestosterone. J Biol Chem. 2007;282(35):25801–25816. doi:10.1074/jbc.M703268200 2. Hur E, Pfaff SJ, Payne ES, Grøn H, Buehrer BM, Fletterick RJ. Recognition and accommodation at the androgen receptor coactivator binding interface. PLoS Biol. 2004;2(9):E274. doi:10.1371/journal.pbio.0020274