ER alpha(LBD) His&Sumo Tag Protein, Human

The ligand-binding domain (LBD) of the estrogen receptor (ER) is located at the C-terminus of the protein and consists of approximately 250 amino acids, forming a three-layer helical bundle containing 12 α-helices, among which helix 12 (H12) serves as a conformational switch. Its function is to bind ligands such as estradiol; upon agonist binding, H12 caps the ligand-binding pocket and exposes the AF-2 coactivator-binding site, thereby initiating transcription. Clinically, the LBD is a core target of endocrine therapy, but mutations such as Y537S and D538G can stabilize the active conformation, leading to constitutive receptor activation and resistance to SERDs such as fulvestrant. PROTACs developed based on the LBD structure, such as Vepdegestrant, employ an event-driven degradation mechanism to effectively eliminate mutant ER, offering a new strategy for refractory breast cancer.