3ert
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HUMAN ESTROGEN RECEPTOR ALPHA LIGAND-BINDING DOMAIN IN COMPLEX WITH 4-HYDROXYTAMOXIFEN
OverviewOverview
Ligand-dependent activation of transcription by nuclear receptors (NRs) is, mediated by interactions with coactivators. Receptor agonists promote, coactivator binding, and antagonists block coactivator binding. Here we, report the crystal structure of the human estrogen receptor alpha (hER, alpha) ligand-binding domain (LBD) bound to both the agonist, diethylstilbestrol (DES) and a peptide derived from the NR box II region, of the coactivator GRIP1 and the crystal structure of the hER alpha LBD, bound to the selective antagonist 4-hydroxytamoxifen (OHT). In the, DES-LBD-peptide complex, the peptide binds as a short alpha helix to a, hydrophobic groove on the surface of the LBD. In the OHT-LBD complex, helix 12 occludes the coactivator recognition groove by mimicking the, interactions of the NR box peptide with the LBD. These structures reveal, the two distinct mechanisms by which structural features of OHT promote, this "autoinhibitory" helix 12 conformation.
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
3ERT is a Single protein structure of sequence from Homo sapiens with OHT as ligand. This structure superseeds the now removed PDB entry 2ERT. The following page contains interesting information on the relation of 3ERT with [Estrogen Receptor]. Full crystallographic information is available from OCA.
ReferenceReference
The structural basis of estrogen receptor/coactivator recognition and the antagonism of this interaction by tamoxifen., Shiau AK, Barstad D, Loria PM, Cheng L, Kushner PJ, Agard DA, Greene GL, Cell. 1998 Dec 23;95(7):927-37. PMID:9875847
Page seeded by OCA on Mon Nov 12 23:48:08 2007