Allosteric cross-domain signaling

Our lab has discovered the dynamic interactions between the flexible ligand-binding domain (LBD) and DNA-binding domain (DBD) of the ER, a member of the nuclear receptor family. Despite long-standing challenges posed by ER’s intrinsic flexibility, we were the first to elucidate the structure and functional role of ER LBD-DBD interactions as a critical ‘allosteric’ channel to transmit hormonal AF2 signaling. This breakthrough also enabled us to develop a novel ER ligand screening assay by targeting the ER domain-domain interface (patent pending).