Fig. 1-12. Schematic representation of the structure of the TSH receptor. (A) Two-dimensional representation with indication of the various domains. The blue boxes correspond to amino-terminal and carboxyl-terminal cysteine-rich portions of the extracellular domain, flanking leucine-rich repeats (LRR, yellow box). (B) General view of the follicle-stimulating hormone receptor (FSHr)-FSH crystal structure as a template to model the interaction between TSH and the TSH receptor (692).The concave inner surface of the receptor, formed by ten leucine rich repeats (LRR2 – 9, shown in blue), contact the middle section of the hormone molecule, both the C-terminal segment of the subunit and the “ seat-belt ” segment of the -subunit (shown in red). (C) EachLRR is composed of theX1-X2-L-X3-L-X4-X5 residues (where X is any amino acid, and L usually is Leu, Ile, or Val), forming the central X2-L-X3-L-X4 a typical beta-strand, while X1 and X5 are parts of the adjacent loops. (D) Molecular model of the transmembrane domain of the TSH receptor, constructed from the crystal structure of bovine rhodopsin. The color code of the -carbon ribbons is: transmembrane helix 1 (crimson), 2 (goldenred), 3 (dark red), 4 (gray), 5 (red), 6 (orange), and 7 (blue), and Helix8 (blue). The structures of available class A rhodopsin-like GPCRs are similar at the transmembrane domain.