Crystal structure of endocrine-disrupting chemical bisphenol A and estrogen-related receptor γ

The human estrogen-related receptor γ (ERRγ) is an orphan nuclear receptor. The ERRγ behaves as a constitutive activator of transcription and plays a key role in controlling mitochondrial energy production and energy metabolism. Bisphenol A (BPA) is used mainly in producing polycarbonate plastics and epoxy resins, but it is known as an endocrine disruptor and strongly binds to ERRγ. We determined the crystal structure of ERRγ in complex with BPA. Our structure revealed the molecular mechanism of BPA recognition by ERRγ, in which BPA is well anchored to its ligand-binding pocket. Our structure is the first report of the complex between a nuclear receptor and endocrine disruptor BPA. This structural analysis had a profound impact on subsequent studies of endocrine disruptors.