Intracellular receptors: Difference between revisions

Discovered in 1996, <scene name='48/483891/Initial_view/1'>estrogen receptor beta</scene> (ER-β) is one of the two isoforms of the estrogen receptor, a ligand-activated transcription factor which regulates the biological effects of the steroid hormone 17 beta-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 beta</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<ref>PMID: 1552044</ref>. This activates expression of reporter genes containing estrogen response elements. Genistein is a phytoestrogen with structural similarity to estrogen which competes for estrogen receptors. This ligand can increase growth rate of estrogen receptor expressing breast cancers and can inhibit immune response to cancer cells, allowing them to proliferate depending on its concentration. In normal tissues, ER-β is an essential receptor for maintaining the functions of vital organs, and may also help regulate apoptosis, control antioxidant gene expression, and modulate immune responses<ref>PMID: 1552044</ref>.

Although estrogen receptor beta is widely expressed, it is not the primary estrogen receptor in most tissues. As a result, it has become a target for drug delivery, especially since it is 40x more selective for genistein than the α isoform. This enhanced selectivity may be caused by differences in residues <scene name='48/483891/Met336_ile373/2'>336 and 373</scene><ref>PMID: 15576033</ref> between the two isoforms, allowing ER-β to accommodate more polar substituents in its binding pocket. ER-β differs greatly from ER-α at the N-terminal domains<ref>PMID: 12878140</ref> , which can be seen located at opposite ends from the C termini in this <scene name='48/483891/Rainbow/1'>rainbow representation</scene>. The protein is composed of three sections: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain.

The genistein-estrogen receptor beta complex is a heterotetramer consisting of two estrogen receptor beta (ERβ) chains and 2 steroid receptor coactivator-1 chains. Each ERβ contains several domains with specific functions: an N-terminal domain (NTD), a {{Template:ColorKey Composition DNA}}-binding domain (DBD), a flexible hinge region and a C-terminal {{Template:ColorKey Composition Ligand}}-binding domain (LBD). The complex overall is about <scene name='48/483891/Erhelices/1'>66% helical (10 helices; 160 residues) and 3% beta sheet (2 strands; 9 residues)</scene><ref>PMID: 20922740</ref>.