Decoding the Mechanism of "Getting Used" to Noise at the Molecular Level: A New Strategy to Turn Down Inflammation Volume - Treatment Targets for Inflammation and Hearing Have Come Much Closer

The research team at OHSU visualized at the atomic level the P2X receptor group that detects extracellular ATP, specifically P2X7, which is involved in inflammation, and P2X2, which is related to hearing. In human P2X7, they identified an allosteric binding pocket and CHS binding mode different from those in animals, and based on this, they designed a novel human-optimized inhibitor called UB-MBX-46. They demonstrated that it can precisely block human P2X7 with sub-nanomolar selectivity. Meanwhile, for P2X2, they obtained the 3D structures of its resting state and desensitized state after ATP binding, clarifying the positioning of mutations related to hearing loss. Both findings provide a foundation for targeted drug discovery for inflammatory diseases and hearing loss. The research is supported by explanations on Phys.org and papers in Nature Communications/PNAS.