ABSTRACT
The thyrotropin receptor (TSHR) not only plays a crucial role in thyroid physiology but also is the main antigen directly involved in the pathogenesis of Graves’ disease (reviewed in ref. 1). TSHR belongs to the family of G protein-coupled receptors with a large ectodomain region and a serpentine region that transverses the plasma membrane seven times (2-5). Regarding its subunit structure, the TSHR is the only member of the glycoprotein hormone receptor that cleaves on the cell surface of mammalian cells into two subunits: an A subunit present within the ectodomain region linked by disulfide bonds to a B subunit (6-8). The TSHR ectodomain is highly glycosylated (9) and contains the binding sites for the thyroid-stimulating hormone (TSH) as well as for stimulating and blocking TSHR autoantibodies (10,11). These binding sites involve mutiple and discontinous regions throughout the ectodomain (10,11).
