Abstract
Extensive mutagenesis studies of the long extracellular domain of the TSH receptor (TSHR) revealed important residues (Cys-301, Tyr-385 and Cys-390) for binding of TSH in its C-terminal region. These two cysteines were postulated to form a disulfide bond catalyzed by TSH.
On the other hand, binding sites of a thyroid stimulating antibody were located in the N-terminal region of the extracellular domain.
The long extracellular domain of the TSHR has 5 or 6 possible asparagine-linked glycosylation sites. However, only two sites are essential for the expression of a functional receptor among them. Although point mutation at residue 113 of the human TSHR lost TSH binding, the equivalent mutation of the rat TSHR did not, implying a difference in the significance of sugar chains among species.
G protein interaction sites have recently been defined by mutagenesis studies. However, the details of how TSH binding to the long extracellular domain causes conformational change in the transmembrane domain remains to be elucidated.
