Sandbox Reserved 1780

Active and Inactive Form

The TSHR protein exists in two states, active and inactive. The sticks out from the cell membrane into the space outside the cell. The contains 7 alpha helices that reside within the cell membrane. The exists when bound to the thyroid stimulating hormone (TSH). One proposed mechanism for the transition from the active to inactive describes that in its natural state, the TSHR ECD can spontaneously transition to the up state, leading to constitutive activity. In this active state, TSH will bind and keep the active state in the up position because of clash with the cell membrane.^[1] Conformational change of ECD allows for signal transduction through the TM and into the cell. ​

Figure 1: Inactive form of the thyrotropin receptor shown in blue. Active form of the thyrotropin receptor shown in green. Extracellular domain rotates about the dynamic hinge region. Transmembrane domain also sees some movement.