Sandbox Reserved 1774

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The TSHR exists in two states: <scene name='95/952702/Overlay/2'>active and inactive </scene>. When the extracellular domain is hinged down, the receptor is inactive and no signaling activation occurs. Upward movement of the ECD into the active states pulls on the transmembrane helices to activate the G-protein, which in turns set off an intracellular signaling cascade that ends in transcriptional activation of thyroid hormones, including T3 and T4 (Fig. __).
The TSHR exists in two states: <scene name='95/952702/Overlay/2'>active and inactive </scene>. When the extracellular domain is hinged down, the receptor is inactive and no signaling activation occurs. Upward movement of the ECD into the active states pulls on the transmembrane helices to activate the G-protein, which in turns set off an intracellular signaling cascade that ends in transcriptional activation of thyroid hormones, including T3 and T4 (Fig. __).
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The hinge motion of the TSHR is made possible by the hinge region structure. Deformation of the hinge region accommodates up-and-down rotation of the extracellular domain as a rigid body, which hinges approximately 55 degrees around an imaginary axis <ref name="Faust">PMID:35940205</ref> [[Image:TSHR_MorphBetterAngle.mp4|Figure 1]]. As the receptor transitions towards its active state, stretching of the hinge region leads to shifting of the transmembrane helices. Additionally, the hinge region itself serves as an agonist of TSHR activation through intermolecular interactions with the transmembrane domain in the active state. While switching between the active and inactive states is spontaneous, these hinge interactions favor the active conformation, as does binding of the TSH ligand <ref name="Faust">PMID:35940205</ref>. To fully understand these stabilizing interactions, a deeper discussion of hinge region anatomy is warranted.
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The hinge motion of the TSHR is made possible by the hinge region structure. Deformation of the hinge region accommodates up-and-down rotation of the extracellular domain as a rigid body, which hinges approximately 55 degrees around an imaginary axis <ref name="Faust">PMID:35940205</ref> [[Image:TSHR_MorphBetterAngle_GIF.gif|Figure 2: Hinge region (blue) accomondates rigid movement of the ECD (green) towards and away from the TMD (pink). ]]. As the receptor transitions towards its active state, stretching of the hinge region leads to shifting of the transmembrane helices. Additionally, the hinge region itself serves as an agonist of TSHR activation through intermolecular interactions with the transmembrane domain in the active state. While switching between the active and inactive states is spontaneous, these hinge interactions favor the active conformation, as does binding of the TSH ligand <ref name="Faust">PMID:35940205</ref>. To fully understand these stabilizing interactions, a deeper discussion of hinge region anatomy is warranted.
=== Stabilizing Interactions in the Hinge Favor Signaling Activation ===
=== Stabilizing Interactions in the Hinge Favor Signaling Activation ===

Revision as of 01:31, 9 April 2023

This Sandbox is Reserved from February 27 through August 31, 2023 for use in the course CH462 Biochemistry II taught by R. Jeremy Johnson at the Butler University, Indianapolis, USA. This reservation includes Sandbox Reserved 1765 through Sandbox Reserved 1795.
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