1L2I

Human Estrogen Receptor alpha Ligand-binding Domain in Complex with (R,R)-5,11-cis-diethyl-5,6,11,12-tetrahydrochrysene-2,8-diol and a Glucocorticoid Receptor Interacting Protein 1 NR box II Peptide

Summary for 1L2I

• Entry DOI: 10.2210/pdb1l2i/pdb
• Related: 1L2J 3ERD
• Descriptor: ESTROGEN RECEPTOR, GLUCOCORTICOID RECEPTOR-INTERACTING PROTEIN 1, CHLORIDE ION, ... (5 entities in total)
• Functional Keywords: nuclear receptor, transcription factor, estrogen, agonist, coactivator, transcription receptor-coactivator complex, transcription receptor/coactivator
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 63652.55

Authors

Shiau, A.K.,Barstad, D.,Radek, J.T.,Meyers, M.J.,Nettles, K.W.,Katzenellenbogen, B.S.,Katzenellenbogen, J.A.,Agard, D.A.,Greene, G.L. (deposition date: 2002-02-21, release date: 2002-05-01, Last modification date: 2023-08-16)

Primary citation

Shiau, A.K.,Barstad, D.,Radek, J.T.,Meyers, M.J.,Nettles, K.W.,Katzenellenbogen, B.S.,Katzenellenbogen, J.A.,Agard, D.A.,Greene, G.L.
Structural characterization of a subtype-selective ligand reveals a novel mode of estrogen receptor antagonism.
Nat.Struct.Biol., 9:359-364, 2002

PubMed Abstract: The R,R enantiomer of 5,11-cis-diethyl-5,6,11,12-tetrahydrochrysene-2,8-diol (THC) exerts opposite effects on the transcriptional activity of the two estrogen receptor (ER) subtypes, ER alpha and ER beta. THC acts as an ER alpha agonist and as an ER beta antagonist. We have determined the crystal structures of the ER alpha ligand binding domain (LBD) bound to both THC and a fragment of the transcriptional coactivator GRIP1, and the ER beta LBD bound to THC. THC stabilizes a conformation of the ER alpha LBD that permits coactivator association and a conformation of the ER beta LBD that prevents coactivator association. A comparison of the two structures, taken together with functional data, reveals that THC does not act on ER beta through the same mechanisms used by other known ER antagonists. Instead, THC antagonizes ER beta through a novel mechanism we term 'passive antagonism'.

PubMed: 11953755

Experimental method

X-RAY DIFFRACTION (1.95 Å)