3ERT

HUMAN ESTROGEN RECEPTOR ALPHA LIGAND-BINDING DOMAIN IN COMPLEX WITH 4-HYDROXYTAMOXIFEN

Replaces:  2ERT

Summary for 3ERT

• Entry DOI: 10.2210/pdb3ert/pdb
• Descriptor: PROTEIN (ESTROGEN RECEPTOR ALPHA), 4-HYDROXYTAMOXIFEN (3 entities in total)
• Functional Keywords: nuclear receptor, transcription factor, estrogen, antagonist
• Biological source: Homo sapiens (human)
• Cellular location: Isoform 1: Nucleus. Isoform 3: Nucleus: P03372
• Total number of polymer chains: 1
• Total formula weight: 30237.73

Authors

Shiau, A.K.,Barstad, D.,Loria, P.M.,Cheng, L.,Kushner, P.J.,Agard, D.A.,Greene, G.L. (deposition date: 1999-03-30, release date: 1999-04-08, Last modification date: 2023-09-06)

Primary citation

Shiau, A.K.,Barstad, D.,Loria, P.M.,Cheng, L.,Kushner, P.J.,Agard, D.A.,Greene, G.L.
The structural basis of estrogen receptor/coactivator recognition and the antagonism of this interaction by tamoxifen.
Cell(Cambridge,Mass.), 95:927-937, 1998

PubMed Abstract: 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.

PubMed: 9875847
DOI: 10.1016/S0092-8674(00)81717-1

Experimental method

X-RAY DIFFRACTION (1.9 Å)