Figure 1.

(a) Schematic representation of the WT TSHR that undergoes cleavage into an extracellular A subunit and a serpentine, membrane-spanning B subunit. The cleavage process involves excision of a C peptide region (reviewed in ref. 2). (b) TSHR modified by deletion of amino acid residues 317–366 and substitution of GQE367-369NET. This receptor (TSHR-D1NET) undergoes minimal cleavage into subunits (15). (c) TSHR-289 is the TSHR truncated after amino acid 289, at the approximate region of spontaneous intramolecular cleavage into subunits (14). Consequently, TSHR-289 approximates the free, or shed, A subunit. (Adapted from ref. 9.)