Monitoring ligand-mediated helix 12 transitions within the human estrogen receptor α using bipartite tetracysteine display

2020 ◽  
Vol 18 (31) ◽  
pp. 6063-6071
Author(s):  
Ranju Pokhrel ◽  
Tang Tang ◽  
Justin M. Holub
Keyword(s):  
Estrogen Receptor ◽  
Ligand Binding ◽  
Estrogen Receptor Α ◽  
Fluorescent Labeling ◽  
Binding Domain ◽  
Ligand Binding Domain ◽  
Human Estrogen Receptor ◽  
Helix 12

Fluorescent labeling coupled with bipartite tetracysteine display enables the surveillance of ligand-mediated helix 12 transitions within the estrogen receptor α ligand-binding domain.

scholarly journals Identification of Regions within the F Domain of the Human Estrogen Receptor α that Are Important for Modulating Transactivation and Protein-Protein Interactions

2007 ◽  
Vol 21 (4) ◽  
pp. 829-842 ◽  
Author(s):  
Akiko Koide ◽  
Changqing Zhao ◽  
Misuzu Naganuma ◽  
Judith Abrams ◽  
Sarah Deighton-Collins ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Ligand Binding ◽  
Protein Interactions ◽  
Mammalian Cells ◽  
Steroid Receptor ◽  
Estrogen Receptor Α ◽  
Binding Domain ◽  
Ligand Binding Domain ◽  
Steroid Receptor Coactivator ◽  
Human Estrogen Receptor

Abstract The estrogen receptor (ER)α is a biologically and clinically important ligand-modulated transcription factor. The F domain of the ERα modulates its functions in a ligand-, promoter-, and cell-specific manner. To identify the region(s) responsible for these functions, we characterized the effects of serial truncations within the F domain. We found that truncating the last 16 residues of the F domain altered the activity of the human ERα (hERα) on an estrogen response element-driven promoter in response to estradiol or 4-hydroxytamoxifen (4-OHT), its sensitivity to overexpression of the coactivator steroid receptor coactivator-1 in mammalian cells, and its interaction with a receptor-interacting domain of the coactivator steroid receptor coactivator-1 or engineered proteins (“monobodies”) that specifically bind to ERα/ligand complexes in a yeast two-hybrid system. Most importantly, the ability of the ER to induce pS2 was reduced in MDA-MB-231 cells stably expressing this truncated ER vs. the wild-type ER. The region includes a distinctive segment (residues 579–584; LQKYYIT) having a high content of bulky and/or hydrophobic amino acids that was previously predicted to adopt a β-strand-like structure. As previously reported, removal of the entire F domain was necessary to eliminate the agonist activity of 4-OHT. In addition, mutation of the vicinal glycine residues between the ligand-binding domain and F domains specifically reduced the 4-OHT-dependent interactions of the hERα ligand-binding domain and F domains with monobodies. These results show that regions within the F domain of the hERα selectively modulate its activity and its interactions with other proteins.

scholarly journals Correction to: Targeted degradation of activating estrogen receptor α ligand-binding domain mutations in human breast cancer

2020 ◽  
Vol 180 (3) ◽  
pp. 623-623
Author(s):  
Thomas L. Gonzalez ◽  
Molly Hancock ◽  
Siqi Sun ◽  
Christina L. Gersch ◽  
Jose M. Larios ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Ligand Binding ◽  
Human Breast Cancer ◽  
Estrogen Receptor Α ◽  
Binding Domain ◽  
Ligand Binding Domain ◽  
Human Breast

Targeted degradation of activating estrogen receptor α ligand-binding domain mutations in human breast cancer

2020 ◽  
Vol 180 (3) ◽  
pp. 611-622 ◽  
Author(s):  
Thomas L. Gonzalez ◽  
Molly Hancock ◽  
Siqi Sun ◽  
Christina L. Gersch ◽  
Jose M. Larios ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Ligand Binding ◽  
Human Breast Cancer ◽  
Estrogen Receptor Α ◽  
Binding Domain ◽  
Ligand Binding Domain ◽  
Human Breast
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