Fig. 1.

a A computer generated model of the TSHR based on the crystal structure of the ectodomain with the 7 transmembrane domain structure derived from the rhodopsin receptor crystal. The large ectodomain consists of 9 leucine-rich repeats (LRRs), which form a characteristic “horse shoe” shaped structure with a concave inner surface which harbors the major ligand and TSHR-Ab binding regions. The cleavage region and unique 50 amino acids cleaved region in the ectodomain, of unknown structure, is shown in gray and is a unique characteristic of the TSHR. b A schematic model of the TSHR to illustrate the multiple domains, subunits and epitope distributions containing different amino acid residues. TSHR stimulating and blocking antibodies are directed to the conformational epitopes whereas cleavage antibodies are directed at linear epitopes, mainly targeting the cleavage region.