Two possible structural configurations of TSH receptor. (a) The uncleaved receptor is shown with a “buried” structure. The ectodomain and transmembrane interactions result in a “closed” conformation (connecting dotted lines). (b) Cleavage may induce an “open” conformation, a step that is thought to be a precondition for subsequent changes in receptor localization and activity, as described in the text and shown in Figure 2. This figure is adapted from ref. 25 with permission.