Fig. 1

Comparative models of the structure of the transmembrane domain (TMD) of the thyroid-stimulating hormone receptor (TSHR) in three different orientations related by 90° rotations along a vertical axis. TMD_I is based on 16 G protein-coupled receptor (GPCR) structures in their inactive conformations. TMD_In is based on three GPCR structures in their inactive conformations. TMD_Ac is based on the same three GPCRs as TMD_In, but in their active conformations. Transmembrane helices (TM), extracellular loops (ECL), intracellular loops (ICL), C-terminal tail (C-tail) and N- and C-termini (N, C) are marked. Sequence motifs (blue background circles) and structural features (yellow background circles) of the transmembrane domain of the TSH receptor in their active and inactive conformations are shown. Ionic lock (1), N⁶⁷⁴PxxY⁶⁷⁸ motif (2) in TM7, N⁴⁵⁵LxxxD⁴⁶⁰ motif (3) in TM2 and C⁶³⁶MxP⁶³⁹ motif (4) in TM6. Alpha bulge (5) in TM2, proline distortion (6) in TM4, proline kink (7) in TM6 and proline kink (8) in TM7. The G-protein binding site is clearly visible at the cytoplasmic end of the active conformation.