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From Proteopedia
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<Structure load='1x7j' size='300' frame='true' align='right' caption='1x7j, Beta estrogen receptor (grey and green) with transcription intermediate factor-2 peptide (pink and yellow) and genistein' scene='Insert optional scene name here' /> | <Structure load='1x7j' size='300' frame='true' align='right' caption='1x7j, Beta estrogen receptor (grey and green) with transcription intermediate factor-2 peptide (pink and yellow) and genistein' scene='Insert optional scene name here' /> | ||
| - | The estrogen receptor beta 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. Genistein is a phytoestrogen with structural similarity to estrogen and 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. | + | The estrogen receptor beta (initial view) 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. Genistein is a phytoestrogen with structural similarity to estrogen and 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 this rainbow representation the N and C termini are at the bottom of the structure; this is where the connections to the transmembrane helices have been truncated. |
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Revision as of 03:01, 13 March 2015
| This Sandbox is Reserved from January 19, 2016, through August 31, 2016 for use for Proteopedia Team Projects by the class Chemistry 423 Biochemistry for Chemists taught by Lynmarie K Thompson at University of Massachusetts Amherst, USA. This reservation includes Sandbox Reserved 425 through Sandbox Reserved 439. |
Contents |
Estrogen receptor beta/genistein complex
Introduction
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The estrogen receptor beta (initial view) 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. Genistein is a phytoestrogen with structural similarity to estrogen and 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 this rainbow representation the N and C termini are at the bottom of the structure; this is where the connections to the transmembrane helices have been truncated.
Overall Structure
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Estrogen receptor beta and genistein complex consists of 4 chains. The phytoestrogen, genistein, is completely buried in the hydrophobic core of the protein.
Estrogen receptor beta contains several domains for different functions. Its N-terminal domain (NTD) consists most of random coils and a small portion of helices and sheets. This lack of structure allows it to recruit and bond proper interaction partners. Within the NTD, the A and B domains can transactivate transcription without binding estrogen, and the C domain or the DNA binding domain (DBD) that binds estrogen response elements of DNA. The D domain is a hinge region connecting DBD to the E domain, ligand binding domain (LBD), at the C terminal. LBD binds coregulatory proteins, corepressors and coactivators.
Binding Interactions
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Genistein's bicyclic form allows it to hydrogen bond on opposite sides with the hydroxyls of the histidine groups on the receptor. (His475) Its binding to the receptor causes a conformational change and activates the receptor resulting in either up-regulation or down-regulation of gene expression.
Additional Features
In order for the estrogen receptor beta genistein to bind to a receptor and activate it there must be stabilization by a coactivator. The coactivator increases the gene expression and with this increase allows it to bind to an activator group consisting of a DNA binding domain. The estrogen receptor is found to be comprised of a dimer attached to a ligand and coactivator peptide which helps to stabilize the structure of each monomer. The conformational state of helix-12 can be modified by the binding of the coactivator.
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Quiz Question 1
Quiz Question 2
See Also
- UvrABC
- Androgen receptor
- Estrogen receptor
- Estrogen-related receptor
- Nuclear receptor coactivator
- Hormone
- Glycogen synthase kinase 3
- CREB-binding protein
Credits
Introduction - Brian Cain
Overall Structure - Anna Novikova
Drug Binding Site - name of team member
Additional Features - William Doherty
Quiz Question 1 - James Conner
Quiz Question 2 - name of team member
