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

The human estrogen-related receptor gamma (ERR gamma) is an orphan nuclear receptor. The ERR gamma 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 ERR gamma. We determined the crystal structure of ERR gamma in complex with BPA. Our structure revealed the molecular mechanism of BPA recognition by ERR gamma, 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.

Automated summary

The human estrogen-related receptor gamma (ERR gamma) is a constitutive activator of transcription and plays a key role in mitochondrial energy production and energy metabolism. Bisphenol A (BPA), known as an endocrine disruptor, strongly binds to ERR gamma. The crystal structure of ERR gamma in complex with BPA reveals the molecular mechanism of BPA recognition, providing important insights for future studies on endocrine disruptors.