3ert | pdb_00003ert

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

spinqualitylabelsall models 3ert, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3ert is a 1 chain structure with sequence from Human. This structure supersedes the now removed PDB entry 2ert. The September 2003 RCSB PDB Molecule of the Month feature on Estrogen Receptor by David S. Goodsell is 10.2210/rcsb_pdb/mom_2003_9. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: OHT Gene: ESTROGEN RECEPTOR ALPHA (HUMAN) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [ESR1_HUMAN] Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Isoform 3 is involved in activation of NOS3 and endothelial nitric oxide production. Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full length receptor. Isoform 3 can bind to ERE and inhibit isoform 1. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Estrogen receptor Estrogen receptor 3D structures

Proteopedia Page Contributors and Editors (what is this?)

OCA