Sandbox Reserved 1779: Difference between revisions

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=== Active and Inactive Form ===

[[Image:Morphmembrane.png|450 px|right|thumb|Figure 2: Inactive form of the thyrotropin receptor shown in blue (PDB: 7T9M). Active form of the thyrotropin receptor shown in green (PDB: 7T9I).]]

The TSHR protein exists in two states: active and inactive (Figure 2) (GREEN LINK ?). ~~The <scene name='95/952708/Tshr_chainr/4'>TSHR active form</scene> (GREEN LINK take away extra molecules) exists in dynamic equilibrium where <scene name='95/952708/Tsh_7t9i/1'>~~TSH~~</scene>~~ (GREEN LINK ~~make TSH one color~~) ~~binding favors the active state. In this active state, TSH~~ will bind and keep the active state in the up position ~~because~~ of clashes between bound TSH and the cell membrane.<ref name="Faust" />. Glycosylations of ~~the~~ Asn52 residue cause this clash (GREEN LINK) on the <scene name='95/952707/Tsh_7t9i/1'>α-subunit of TSH</scene>. ~~The addition of N-acetyl glucosamine modifications creates steric clashes between TSH and the cell membrane, keeping TSHR in the active state.~~

The TSHR protein exists in dynamic equilibrium between two states: active and inactive (Figure 2) (GREEN LINK). TSH (GREEN LINK) will bind and keep the active state in the up position as a result of clashes between bound TSH and the cell membrane.<ref name="Faust" />. Glycosylations of an Asn52 residue cause this clash (GREEN LINK) on the <scene name='95/952707/Tsh_7t9i/1'>α-subunit of TSH</scene>.

===Structural Overview===

The thyrotropin receptor has an extracellular domain (ECD) that is composed of a <scene name='95/952709/Lrrd_real/2'>leucine rich repeat domain (LRRD)</scene> as well as a hinge region. This <scene name='95/952709/Hinge_region_real/2'>hinge region</scene> links the ECD to the seven transmembrane helices <scene name='95/952709/7tm_helices/4'>(7TM domain)</scene>, which span from the extracellular domain to the intracellular domain <ref name= "Keinau et al.">Kleinau, G., Worth, C. L., Kreuchwig, A., Biebermann, H., Marcinkowski, P., Scheerer, P., & Krause, G. (2017). Structural–functional features of the thyrotropin receptor: A class A G-protein-coupled receptor at work. Frontiers in Endocrinology, 8. https://doi.org/10.3389/fendo.2017.00086</ref>. Thyrotropin binding causes a conformational change in the ECD that is transduced through the transmembrane helices. In the active state, the ECD is in the "up" position, while in the inactive state, the ECD is in the "down" state, closer to the cell membrane. A "push-pull" mechanism is proposed to be responsible for the ECD's conformational change between active and inactive states. In the "push" model, TSH binds to the receptor and sterically clashes with the cellular membrane forcing the ECD up away from the membrane. In the pull model, a short α-helix interacts with TSH to pull the ECD up. The active (up) form of the ECD causes a conformation shift in the TMD which causes differential interactions with a heterotrimeric <scene name='95/952709/G_protein/2'>G-protein</scene>, initiating intracellular signaling<ref name="Duan et al.">PMID:35940204</ref>.

Sandbox Reserved 1779: Difference between revisions

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@@ Line 9: / Line 9: @@
 === Active and Inactive Form ===
 [[Image:Morphmembrane.png|450 px|right|thumb|Figure 2: Inactive form of the thyrotropin receptor shown in blue (PDB: 7T9M). Active form of the thyrotropin receptor shown in green (PDB: 7T9I).]]
-The TSHR protein exists in two states: active and inactive (Figure 2) (GREEN LINK ?). The <scene name='95/952708/Tshr_chainr/4'>TSHR active form</scene> (GREEN LINK take away extra molecules) exists in dynamic equilibrium where <scene name='95/952708/Tsh_7t9i/1'>TSH</scene> (GREEN LINK make TSH one color) binding favors the active state. In this active state, TSH will bind and keep the active state in the up position because of clashes between bound TSH and the cell membrane.<ref name="Faust" />. Glycosylations of the Asn52 residue cause this clash (GREEN LINK) on the <scene name='95/952707/Tsh_7t9i/1'>α-subunit of TSH</scene>. The addition of N-acetyl glucosamine modifications creates steric clashes between TSH and the cell membrane, keeping TSHR in the active state.
+The TSHR protein exists in dynamic equilibrium between two states: active and inactive (Figure 2) (GREEN LINK). TSH (GREEN LINK) will bind and keep the active state in the up position as a result of clashes between bound TSH and the cell membrane.<ref name="Faust" />. Glycosylations of an Asn52 residue cause this clash (GREEN LINK) on the <scene name='95/952707/Tsh_7t9i/1'>α-subunit of TSH</scene>.
 ===Structural Overview===
 The thyrotropin receptor has an extracellular domain (ECD) that is composed of a <scene name='95/952709/Lrrd_real/2'>leucine rich repeat domain (LRRD)</scene> as well as a hinge region. This <scene name='95/952709/Hinge_region_real/2'>hinge region</scene> links the ECD to the seven transmembrane helices <scene name='95/952709/7tm_helices/4'>(7TM domain)</scene>, which span from the extracellular domain to the intracellular domain <ref name= "Keinau et al.">Kleinau, G., Worth, C. L., Kreuchwig, A., Biebermann, H., Marcinkowski, P., Scheerer, P., &amp; Krause, G. (2017). Structural–functional features of the thyrotropin receptor: A class A G-protein-coupled receptor at work. Frontiers in Endocrinology, 8. https://doi.org/10.3389/fendo.2017.00086</ref>. Thyrotropin binding causes a conformational change in the ECD that is transduced through the transmembrane helices. In the active state, the ECD is in the "up" position, while in the inactive state, the ECD is in the "down" state, closer to the cell membrane. A "push-pull" mechanism is proposed to be responsible for the ECD's conformational change between active and inactive states. In the "push" model, TSH binds to the receptor and sterically clashes with the cellular membrane forcing the ECD up away from the membrane. In the pull model, a short α-helix interacts with TSH to pull the ECD up. The active (up) form of the ECD causes a conformation shift in the TMD which causes differential interactions with a heterotrimeric <scene name='95/952709/G_protein/2'>G-protein</scene>, initiating intracellular signaling<ref name="Duan et al.">PMID:35940204</ref>.