2JF9

ESTROGEN RECEPTOR ALPHA LBD IN COMPLEX WITH A TAMOXIFEN-SPECIFIC PEPTIDE ANTAGONIST

Summary for 2JF9

• Entry DOI: 10.2210/pdb2jf9/pdb
• Related: 1A52 1AKF 1ERE 1ERR 1G50 1GWQ 1GWR 1HCP 1HCQ 1L2I 1PCG 1QKT 1QKU 1R5K 1SJ0 1UOM 1X7E 1X7R 1XP1 1XP6 1XP9 1XPC 1XQC 1YIM 1YIN 1ZKY 2AYR 2B1V 2BJ4 2FAI 2JFA 3ERD 3ERT
• Descriptor: ESTROGEN RECEPTOR, AB5 PEPTIDE, 4-HYDROXYTAMOXIFEN, ... (7 entities in total)
• Functional Keywords: transcription factor, lipid-binding, transcription, transcription regulation, ligand-binding domain (lbd), receptor, zinc-finger, dna-binding, steroid-binding, nuclear receptor, peptide antagonist, metal-binding, nuclear protein, phosphorylation
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Isoform 1: Nucleus . Isoform 3: Nucleus. Nucleus: P03372
• Total number of polymer chains: 6
• Total formula weight: 92318.93

Authors

Heldring, N.,Pawson, T.,McDonnell, D.,Treuter, E.,Gustafsson, J.A.,Pike, A.C.W. (deposition date: 2007-01-29, release date: 2007-02-20, Last modification date: 2023-12-13)

Primary citation

Heldring, N.,Pawson, T.,Mcdonnell, D.,Treuter, E.,Gustafsson, J.A.,Pike, A.C.W.
Structural Insights Into Corepressor Recognition by Antagonist-Bound Estrogen Receptors.
J.Biol.Chem., 282:10449-, 2007

PubMed Abstract: Direct recruitment of transcriptional corepressors to estrogen receptors (ER) is thought to contribute to the tissue-specific effects of clinically important ER antagonists. Here, we present the crystal structures of two affinity-selected peptides in complex with antagonist-bound ERalpha ligand-binding domain. Both peptides adopt helical conformations, bind along the activation function 2 coregulator interaction surface, and mimic corepressor (CoRNR) sequence motif binding. Peptide binding is weak in a wild-type context but significantly enhanced by removal of ER helix 12. This region contains a previously unrecognized CoRNR motif that is able to compete with corepressors for binding to activation function 2, thereby providing a structural explanation for the poor ability of ER to directly interact with classical corepressors. Furthermore, the ability of other sequence motifs to mimic corepressor binding raises the possibility that coregulators do not necessarily require CoRNR motifs for direct recruitment to antagonist-bound ER.

PubMed: 17283072
DOI: 10.1074/JBC.M611424200

Experimental method

X-RAY DIFFRACTION (2.1 Å)