Structure-function relations of the thyrotropin receptor.
The thyrotropin (thyroid-stimulating hormone or TSH) receptor is an amphiphilic membrane component with a relative molecular mass of about 200,000 as judged by gel filtration and an isoelectric point close to pH 5. Analyses with chemical, enzymic and affinity probes indicate that the receptor is a glycoprotein containing a disulphide bridge and that the integrity of the disulphide bond is essential for maintaining the structure of the TSH-binding site. Serum from patients with Graves' disease contains antibodies which inhibit the binding of TSH to its receptor and there is considerable evidence that this effect is due to a direct interaction between the antibodies and the receptor. The antibody-receptor interaction is probably responsible for the TSH agonist properties of Graves' serum and, similarly, the TSH antagonist properties of the sera from a small number of patients can be explained on the basis of antibody-receptor binding. Although TSH and IgG from Graves' disease patients appear to bind to the same receptor, the relationship between the sites for the two substances is not clearly understood. However, Fab fragments of Graves' IgG are as effective as intact IgG in competing with TSH for the receptor and gel filtration and immunoprecipitation studies indicate that the binding of hormone and antibody to the receptor is mutually exclusive. Current evidence suggests therefore that the binding sites for TSH and TSH receptor antibodies are very closely related and may well be identical.
D000918:Antibody Specificity; D001323:Autoantibodies / Q000276:immunology; D006111:Graves Disease / Q000276:immunology; D006801:Humans; D008214:Lymphocytes / Q000276:immunology; D046911:Macromolecular Substances; D011956:Receptors, Cell Surface / Q000276:immunology / Q000502:physiology*; D011989:Receptors, Thyrotropin; D013329:Structure-Activity Relationship; D013961:Thyroid Gland / Q000276:immunology
D001323:Autoantibodies; D046911:Macromolecular Substances; D011956:Receptors, Cell Surface; D011989:Receptors, Thyrotropin