Allosteric cross-domain signaling

Our lab pioneered the characterization of dynamic interactions between the flexible ligand-binding domain (LBD) and DNA-binding domain (DBD) of the estrogen receptor (ER). Despite challenges posed by ER's intrinsic flexibility, we were first to elucidate the structure and functional role of ER LBD-DBD interactions as a critical allosteric channel for hormonal AF2 signaling transmission.

By analyzing domain communication patterns, we uncovered novel protein allostery mechanisms in the ER (Nature Communications 2018). This work revealed asymmetric arrangements between DNA-binding and ligand-binding domains, identifying key interfacial networks that mediate hormone signaling. These discoveries enabled us to develop an innovative ER ligand screening assay targeting the domain-domain interface, with significant translational applications (US Patent 12,135,332, 2024 and bioRxiv 2025).