Figure 4.

Backbone of the molecular SD model and location of signaling-sensitive amino acids in the ECLs. Homology model of the TSHR SD. Close up view of the ECLs that connect the TMHs (ECL1, magenta; ECL2, orange; and ECL3, yellow). The proximity of positions of both inactivating mutations for TSH-mediated signaling (red balls, Cα atom) and positions of CAMs (green balls, Cα atom) reflects the inherent dual functionality in each ECL to facilitate induction and conduction of signaling. Note that positions of inactivating residues (red) are spatially clustered and commonly more exposed to the extracellular regions and thus more available for interactions with the hinge region, whereas those of CAMs (green) are rather constraining the loop conformations.