2BJ4

ESTROGEN RECEPTOR ALPHA LBD IN COMPLEX WITH A PHAGE-DISPLAY DERIVED PEPTIDE ANTAGONIST

Summary for 2BJ4

• Entry DOI: 10.2210/pdb2bj4/pdb
• Related: 1A52 1AKF 1ERE 1ERR 1G50 1GWQ 1GWR 1HCP 1HCQ 1L2I 1PCG 1QKT 1QKU 1R5K 1SJ0 1UOM 1XP1 1XP6 1XP9 1XPC 3ERD 3ERT
• Descriptor: ESTROGEN RECEPTOR, PEPTIDE ANTAGONIST, 4-HYDROXYTAMOXIFEN, ... (5 entities in total)
• Functional Keywords: nuclear receptor, transcription factor, peptide antagonist, ligand-binding domain (lbd), dna-binding, nuclear protein steroid-binding
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Isoform 1: Nucleus . Isoform 3: Nucleus. Nucleus: P03372 P03372
• Total number of polymer chains: 4
• Total formula weight: 60784.95

Authors

Kong, E.,Heldring, N.,Gustafsson, J.A.,Treuter, E.,Hubbard, R.E.,Pike, A.C.W. (deposition date: 2005-01-28, release date: 2005-02-16, Last modification date: 2023-12-13)

Primary citation

Kong, E.,Heldring, N.,Gustafsson, J.A.,Treuter, E.,Hubbard, R.E.,Pike, A.C.W.
Delineation of a Unique Protein-Protein Interaction Site on the Surface of the Estrogen Receptor
Proc.Natl.Acad.Sci.USA, 102:3593-, 2005

PubMed Abstract: Recent studies have identified a series of estrogen receptor (ER)-interacting peptides that recognize sites that are distinct from the classic coregulator recruitment (AF2) region. Here, we report the structural and functional characterization of an ERalpha-specific peptide that binds to the liganded receptor in an AF2-independent manner. The 2-A crystal structure of the ER/peptide complex reveals a binding site that is centered on a shallow depression on the beta-hairpin face of the ligand-binding domain. The peptide binds in an unusual extended conformation and makes multiple contacts with the ligand-binding domain. The location and architecture of the binding site provides an insight into the peptide's ER subtype specificity and ligand interaction preferences. In vivo, an engineered coactivator containing the peptide motif is able to strongly enhance the transcriptional activity of liganded ERalpha, particularly in the presence of 4-hydroxytamoxifen. Furthermore, disruption of this binding surface alters ER's response to the coregulator TIF2. Together, these results indicate that this previously unknown interaction site represents a bona fide control surface involved in regulating receptor activity.

PubMed: 15728727
DOI: 10.1073/PNAS.0407189102

Experimental method

X-RAY DIFFRACTION (2 Å)