2bj4: Difference between revisions
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==Overview== | ==Overview== | ||
Recent studies have identified a series of estrogen receptor, (ER)-interacting peptides that recognize sites that are distinct from the, classic coregulator recruitment (AF2) region. Here, we report the, structural and functional characterization of an ERalpha-specific peptide, that binds to the liganded receptor in an AF2-independent manner. The 2-A, crystal structure of the ER/peptide complex reveals a binding site that is, centered on a shallow depression on the beta-hairpin face of the, ligand-binding domain. The peptide binds in an unusual extended, conformation and makes multiple contacts with the ligand-binding domain., The location and architecture of the binding site provides an insight into, the peptide's ER subtype specificity and ligand interaction preferences., In vivo, an engineered coactivator containing the peptide motif is able to, strongly enhance the transcriptional activity of liganded ERalpha, particularly in the presence of 4-hydroxytamoxifen. Furthermore, disruption of this binding surface alters ER's response to the coregulator, TIF2. Together, these results indicate that this previously unknown, interaction site represents a bona fide control surface involved in, regulating receptor activity. | Recent studies have identified a series of estrogen receptor, (ER)-interacting peptides that recognize sites that are distinct from the, classic coregulator recruitment (AF2) region. Here, we report the, structural and functional characterization of an ERalpha-specific peptide, that binds to the liganded receptor in an AF2-independent manner. The 2-A, crystal structure of the ER/peptide complex reveals a binding site that is, centered on a shallow depression on the beta-hairpin face of the, ligand-binding domain. The peptide binds in an unusual extended, conformation and makes multiple contacts with the ligand-binding domain., The location and architecture of the binding site provides an insight into, the peptide's ER subtype specificity and ligand interaction preferences., In vivo, an engineered coactivator containing the peptide motif is able to, strongly enhance the transcriptional activity of liganded ERalpha, particularly in the presence of 4-hydroxytamoxifen. Furthermore, disruption of this binding surface alters ER's response to the coregulator, TIF2. Together, these results indicate that this previously unknown, interaction site represents a bona fide control surface involved in, regulating receptor activity. | ||
==Disease== | |||
Known diseases associated with this structure: Atherosclerosis, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=133430 133430]], Breast cancer OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=133430 133430]], Estrogen resistance OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=133430 133430]], HDL response to hormone replacement, augmented OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=133430 133430]], Migraine, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=133430 133430]], Myocardial infarction, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=133430 133430]] | |||
==About this Structure== | ==About this Structure== | ||
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[[Category: transcription factor]] | [[Category: transcription factor]] | ||
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Revision as of 21:56, 12 November 2007
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ESTROGEN RECEPTOR ALPHA LBD IN COMPLEX WITH A PHAGE-DISPLAY DERIVED PEPTIDE ANTAGONIST
OverviewOverview
Recent studies have identified a series of estrogen receptor, (ER)-interacting peptides that recognize sites that are distinct from the, classic coregulator recruitment (AF2) region. Here, we report the, structural and functional characterization of an ERalpha-specific peptide, that binds to the liganded receptor in an AF2-independent manner. The 2-A, crystal structure of the ER/peptide complex reveals a binding site that is, centered on a shallow depression on the beta-hairpin face of the, ligand-binding domain. The peptide binds in an unusual extended, conformation and makes multiple contacts with the ligand-binding domain., The location and architecture of the binding site provides an insight into, the peptide's ER subtype specificity and ligand interaction preferences., In vivo, an engineered coactivator containing the peptide motif is able to, strongly enhance the transcriptional activity of liganded ERalpha, particularly in the presence of 4-hydroxytamoxifen. Furthermore, disruption of this binding surface alters ER's response to the coregulator, TIF2. Together, these results indicate that this previously unknown, interaction site represents a bona fide control surface involved in, regulating receptor activity.
DiseaseDisease
Known diseases associated with this structure: Atherosclerosis, susceptibility to OMIM:[133430], Breast cancer OMIM:[133430], Estrogen resistance OMIM:[133430], HDL response to hormone replacement, augmented OMIM:[133430], Migraine, susceptibility to OMIM:[133430], Myocardial infarction, susceptibility to OMIM:[133430]
About this StructureAbout this Structure
2BJ4 is a Single protein structure of sequence from Homo sapiens with OHT as ligand. Structure known Active Site: AC1. Full crystallographic information is available from OCA.
ReferenceReference
Delineation of a unique protein-protein interaction site on the surface of the estrogen receptor., Kong EH, Heldring N, Gustafsson JA, Treuter E, Hubbard RE, Pike AC, Proc Natl Acad Sci U S A. 2005 Mar 8;102(10):3593-8. Epub 2005 Feb 23. PMID:15728727
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