Nuclear receptors: Difference between revisions

Tamoxifen (an ER antagonist) is a drug created to bind ER and inhibit the transcription factor activity of ER. Tamoxifen is larger than the normal hormone ER binds (estradiol); for this reason added with the conformation estrogen receptor takes on, the activation loop is pushed into an inactive conformation. The picture below shows structural differences between the (left/blue) antagonist tamoxifen bound ER and the (right/tan) agonist estradiol bound ER. This blocks ER from giving the signal to grow. Antagonists are generally larger and cause estrogen receptors to be too hindered sterically to be able to bind to the major groove of DNA, inhibiting the receptor. The antagonist bound estrogen receptor is noticeably larger than the agonist bound version. Further inhibition occurs when ER has bound an antagonist ligand. Antagonist bound ER is still brought to Euchromatin in the nucleus. The larger than agonist bound ER ligand chaperon complex is not capable of binding the major groove of DNA, but still occupies the space around specific palindromic sites which ER binds and modifies the transcription of local genes to these palindromic sequence areas. This blocks agonist bound ER from being able to reach these specific palindromic major groove target loci in DNA.

* [[Estrogen receptor#Estrogen receptor α complexed with raloxifene and a corepressor peptide]]

* [[Tamoxifen|Tamoxifen and the Estrogen receptor]]

* [[Student Project 10 for UMass Chemistry 423 Spring 2015]]

<scene name='48/483891/Initial_view/1'>Estrogen receptor β</scene> (ER-β) is 1 of the 2 isoforms of the estrogen receptor, a ligand-activated transcription factor which regulates the biological effects of the steroid hormone 17 β-estradiol, or estrogen, in both males and females. The complex is a hetero-tetrameric assembly consisting of 4 molecules and a ligand: 2 copies of <scene name='48/483891/Erbeta/1'>estrogen receptor β</scene>, 2 copies of <scene name='48/483891/Steroid_receptor/3'>steroid receptor coactivator-1</scene>, and the ligand, <scene name='48/483891/Ligand/3'>Genistein</scene>. Once the ligand is bound, the complex recruits the steroid receptor coactivators, which recruit other proteins to form the transcriptional complex for initiation of transcription. This activates expression of reporter genes containing estrogen response elements. Genistein is a phytoestrogen with structural similarity to estrogen which competes for estrogen receptors.