Related Experiment Video
Updated: Jan 16, 2026

Detecting the Ligand-binding Domain Dimerization Activity of Estrogen Receptor Alpha Using the Mammalian Two-Hybrid Assay
Published on: December 19, 2018
Structural Pharmacology of Estrogen-Related Receptors
Puhan Zhao1,2, Hong Fang1,3, Bahaa Elgendy1,3,2
1Center for Clinical Pharmacology, Washington University School of Medicine in St. Louis and University of Health Sciences & Pharmacy in St. Louis, St. Louis, Missouri 63110, United States.
Abstract:
Estrogen-related receptors (ERRs) are orphan nuclear receptors critical to the regulation of energy metabolism, mitochondrial biogenesis, and tissue-specific transcriptional programs. This review provides a comprehensive structural analysis of ERR isoforms (ERRα, ERRβ, and ERRγ), emphasizing insights from X-ray crystallography and NMR studies. We discuss the ligand-binding domains (LBDs), coactivator and corepressor interactions, and the molecular mechanisms underlying ligand-induced agonism or antagonism. Structural comparisons with estrogen receptors (ERs) reveal key amino acid determinants for ligand selectivity and functional activity. Furthermore, we highlight the development of isoform-selective synthetic ligands, including inverse agonists such as GSK5182, DN200434, and DN201000, with therapeutic potential in metabolic, neurodegenerative, and oncologic diseases. This synthesis of structural data provides a framework for rational drug design targeting ERRs, supporting the development of selective modulators to manipulate ERR signaling in a tissue- and disease-specific manner.
Related Concept Videos
Transducer Mechanism: Nuclear Receptors
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
G Protein-coupled Receptors
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
Internal Receptors
The Two-State Receptor Model
The binding affinity of a drug determines its interaction with...
Types of Receptors: Internal Receptors
Similar to membrane-bound receptors, the binding of a ligand to the intracellular receptor of causes a conformational change in the...
Transducer Mechanism: G Protein–Coupled Receptors
GPCRs are also called heptahelical,...

