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Figure 2 | Thyroid Research

Figure 2

From: Molecular description of non-autoimmune hyperthyroidism at a neonate caused by a new thyrotropin receptor germline mutation

Figure 2

This TSHR homology model (backbone-ribbon presentation) visualizes the potential arrangement of different structural parts at the interface between the extracellular and transmembrane region. Naturally occurring activating mutations in the extracellular loops (ECLs) were reported several times for the TSHR: ECL1- at positions I486 (red boxed) and A485; ECL2 - at position I568; ECL3 at positions N650 and V656 (wild type amino acids are shown as light blue sticks). Interestingly, the wild type amino acids side-chains are exclusively hydrophobic. The tightly embedded structural-functional counterparts of the loops are the extreme N- and C-terminus (green backbone) of the extracellular hinge region (cysteine-boxes 2 and 3 (Cb-2, Cb-3)) were also activating mutations are known (wild type residues as blue sticks). In conclusion these receptor components are sensitive for activation and they are assembled tightly together at the extracellular site of the receptor. Activation of the TSHR on the extracellular site might be related to a relative spatial shift of these determinants to each other, which mediates signal-transduction to the transmembrane helices.

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