Sandbox 27: Difference between revisions

The thyrotropin receptor (or TSH receptor or TSHR) is a member of the G protein-coupled receptor superfamily of integral membrane proteins and is coupled to the Gs protein. It is located on the surface of thyroid follicular cells. Once stimulated by TSH (Thyroid-Stimulating Hormone), THSR activates the production of thyroid hormones: thyroxine (T4) and triiodothyronine (T3).

One of models for the receptor’s activation explains that interactions between ectodomain and extracellular loops would inhibit the activity of serpentine domain in the absence of stimulation. But when TSH is binding to LRD, the ectodomain would have a change of conformation which activates the transduction of signal. <ref> V Vlaeminck-Guillem, G Vassart et S Costagliola, Un modèle d’activation du récepteur de la TSH / A THS receptor activation model, M/S : médecine sciences, vol. 18, n° 12, 2002, p. 1184-1186. </ref>

== Structure of the complexe TSHR – M22 ==

<Structure load='3g04' size='500' frame='true' align='right' caption='M22 autoantibody complexed with TSHR' scene='Insert optional scene name here' | left />

M22 binds to the concave surface of the LRD domain (only a fragment of this domain is represented on the pdb structure: residues 22 to 260 of TSHR)

However we can remark that the M22–TSHR complex involves more strong interactions and fewer hydrophobic interactions than the TSH–TSHR complex. That can explain the effects of the binding of autoantibody like M22. So the idendification of interaction residues and understanding of the mechanism may be useful for developing means of inhibiting TSHR autoantibodies binding.

== Diseases ==

The comprehension of the interactions between the autoantibody and their receptor can be useful for designing a new generation of drugs which will control for example thyroid function by targeting the actions of these autoantibodies responsible for autoimmune diseases.