1QKU

WILD TYPE ESTROGEN NUCLEAR RECEPTOR LIGAND BINDING DOMAIN COMPLEXED WITH ESTRADIOL

Summary for 1QKU

• Entry DOI: 10.2210/pdb1qku/pdb
• Related: 1A52 1AKF 1ERE 1ERR 1HCP 1HCQ 1QKM 1QKN 1QKU 3ERD 3ERT
• Descriptor: ESTRADIOL RECEPTOR, ESTRADIOL (3 entities in total)
• Functional Keywords: nuclear receptor, agonism, antagonism, estradiol receptor, steroid, structural proteomics in europe, spine, structural genomics
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Isoform 1: Nucleus . Isoform 3: Nucleus. Nucleus: P03372
• Total number of polymer chains: 3
• Total formula weight: 86676.33

Authors

Ruff, M.,Gangloff, M.,Eiler, S.,Duclaud, S.,Wurtz, J.M.,Moras, D. (deposition date: 1999-08-05, release date: 2000-08-18, Last modification date: 2024-05-08)

Primary citation

Gangloff, M.,Ruff, M.,Eiler, S.,Duclaud, S.,Wurtz, J.M.,Moras, D.
Crystal structure of a mutant hERalpha ligand-binding domain reveals key structural features for the mechanism of partial agonism.
J. Biol. Chem., 276:15059-15065, 2001

PubMed Abstract: The crystal structure of a triple cysteine to serine mutant ERalpha ligand-binding domain (LBD), complexed with estradiol, shows that despite the presence of a tightly bound agonist ligand, the protein exhibits an antagonist-like conformation, similar to that observed in raloxifen and 4-hydroxytamoxifen-bound structures. This mutated receptor binds estradiol with wild type affinity and displays transcriptional activity upon estradiol stimulation, but with limited potency (about 50%). This partial activity is efficiently repressed in antagonist competition assays. The comparison with available LBD structures reveals key features governing the positioning of helix H12 and highlights the importance of cysteine residues in promoting an active conformation. Furthermore the present study reveals a hydrogen bond network connecting ligand binding to protein trans conformation. These observations support a dynamic view of H12 positioning, where the control of the equilibrium between two stable locations determines the partial agonist character of a given ligand.

PubMed: 11278577
DOI: 10.1074/jbc.M009870200

Experimental method

X-RAY DIFFRACTION (3.2 Å)