Sandbox Reserved 1779: Difference between revisions

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=== Active and Inactive Form ===

[[Image:Finalmorphpic2.png|450 px|right|thumb|Figure 2: Inactive form of the thyrotropin receptor shown in blue (PDB:[https://www.rcsb.org/structure/7T9M 7T9M]). Active form of the thyrotropin receptor shown in green (PDB:[https://www.rcsb.org/structure/7T9I 7T9I]).]]

TSHR exists in dynamic equilibrium between two states: active and inactive (Figure 2). In the active form, the extracellular portion is rotated 55° away from the cell membrane. <scene name='95/952708/Tsh_7t9i/2'>TSH</scene> 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" />. <scene name='95/952708/Tsh_7t9i/4'>Glycolysations of an N52 residue</scene> on the <scene name='95/952707/Tsh_7t9i/1'>α-subunit of TSH</scene> cause this clash.

TSHR exists in dynamic equilibrium between two states: active and inactive (Figure 2). In the active form, the extracellular portion is rotated 55° away from the cell membrane. <scene name='95/952708/Tsh_7t9i/2'>TSH</scene> 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" />. <scene name='95/952708/Tsh_7t9i/5'>Glycolysations of an N52 residue</scene> on the <scene name='95/952707/Tsh_7t9i/1'>α-subunit of TSH</scene> cause this clash.

===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. The <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 ECD to the intracellular loops <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 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 8: / Line 8: @@
 === Active and Inactive Form ===
 [[Image:Finalmorphpic2.png|450 px|right|thumb|Figure 2: Inactive form of the thyrotropin receptor shown in blue (PDB:[https://www.rcsb.org/structure/7T9M 7T9M]). Active form of the thyrotropin receptor shown in green (PDB:[https://www.rcsb.org/structure/7T9I 7T9I]).]]
-TSHR exists in dynamic equilibrium between two states: active and inactive (Figure 2). In the active form, the extracellular portion is rotated 55° away from the cell membrane. <scene name='95/952708/Tsh_7t9i/2'>TSH</scene> 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" />. <scene name='95/952708/Tsh_7t9i/4'>Glycolysations of an N52 residue</scene> on the <scene name='95/952707/Tsh_7t9i/1'>α-subunit of TSH</scene> cause this clash.
+TSHR exists in dynamic equilibrium between two states: active and inactive (Figure 2). In the active form, the extracellular portion is rotated 55° away from the cell membrane. <scene name='95/952708/Tsh_7t9i/2'>TSH</scene> 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" />. <scene name='95/952708/Tsh_7t9i/5'>Glycolysations of an N52 residue</scene> on the <scene name='95/952707/Tsh_7t9i/1'>α-subunit of TSH</scene> cause this clash.
 ===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. The <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 ECD to the intracellular loops <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 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>.