Sandbox Reserved 1791: Difference between revisions

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<scene name=scene name='95/952720/Structure_overview_spins/3'>TSHR has 3 main domains</scene>: Leucine Rich Region Domain (coral), the hinge region (blue-purple), and the transmembrane region(rainbow). The leucine-rich region domain is extracellular. This is where TSH will bind. The hinge region is also extracellular. Conformational changes in this region are responsible for the switch between the active vs inactive state. Finally, the transmembrane region is located within the plasma membrane. Its function is to hold the receptor into the membrane. This domain is also bound to the [https://en.wikipedia.org/wiki/G_protein G-proteins] at the N-terminus. The G-proteins are located on the intracellular side of the plasma membrane. They are important for transmitting the binding signal into the cell, setting off a protein signaling cascade.

=== Transmembrane Region===

<scene name='95/952720/Transmembrane_region_spin/5'>The Transmembrane Region</scene> (<scene name='95/952720/Transmembrane_region_top-view/2'>top-view</scene>) is embedded within the cell membrane. Like other G-protein receptors, it is made up of a 7-pass helix <ref name="Faust"> DOI 10.1038/s41586-022-05159-1</ref>. It is made up of about 284 residues. The transmembrane region is surrounded by a "belt" of <scene name='95/952719/Tmd_cholesterol_spin/3'>15 cholesterols</scene>. When cholesterol binding sites are mutated such that they are unfunctional, TSHR activity decreases. Thus, the cholesterols are important for TSHR function <ref name="Duan"> DOI 10.1038/s41586-022-05173-3</ref>. Additionally, at the N-terminus, the transmembrane region binds to the <scene name='95/~~952720~~/~~Transmembrane_region_spin~~/4'>G-~~proteins~~</scene>, which are located intracellularly.

<scene name='95/952720/Transmembrane_region_spin/5'>The Transmembrane Region</scene> (<scene name='95/952720/Transmembrane_region_top-view/2'>top-view</scene>) is embedded within the cell membrane. Like other G-protein receptors, it is made up of a 7-pass helix <ref name="Faust"> DOI 10.1038/s41586-022-05159-1</ref>. It is made up of about 284 residues. The transmembrane region is surrounded by a "belt" of <scene name='95/952719/Tmd_cholesterol_spin/3'>15 cholesterols</scene>. When cholesterol binding sites are mutated such that they are unfunctional, TSHR activity decreases. Thus, the cholesterols are important for TSHR function <ref name="Duan"> DOI 10.1038/s41586-022-05173-3</ref>. Additionally, at the N-terminus, the transmembrane region binds to the <scene name='95/952719/Tsh-tshr-gs_complex/2'>G-Proteins</scene>, which are located intracellularly.

=== Leucine Rich Domain===

The <scene name='95/952719/Lrrd/1'>Leucine Rich Repeat Domain (LRRD)</scene> is part of the extracellular region of TSHR. It is made up of about 280 different residues. Connected to its C-terminus is the Hinge Region. It is made up of an extensive parallel β-sheet. This β-sheet is where TSH binds and is called the binding pocket<ref name="Duan"> DOI 10.1038/s41586-022-05173-3</ref>. The <scene name='95/952719/Binding_pocket/4'>binding pocket</scene> is a concave structure with many polar residues. This pocket is where the TSH antibody and agonist K1 bind as well as the agonist M22. These structures interact with specific residues to result in a structural change of the molecule. There is a mutation done by N-glycans at asparagine residues that plays a large role in the binding of TSH. The negative charge on these glycans contributes to the polarity of the binding pocket which mediates the binding efficiency of TSH. It has been shown that four of the five N glycan sites must be glycosylated to be in the active form<ref name="Fokina">Fokina, E.F., Shpakov, A.O. Thyroid-Stimulating Hormone Receptor: the Role in the Development of Thyroid Pathology and Its Correction. J Evol Biochem Phys 58, 1439–1454 (2022). [DOI:10.1134/S0022093022050143 https://doi.org/10.1134/S0022093022050143]</ref>.

Sandbox Reserved 1791: Difference between revisions

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 <scene name=scene name='95/952720/Structure_overview_spins/3'>TSHR has 3 main domains</scene>: Leucine Rich Region Domain (coral), the hinge region (blue-purple), and the transmembrane region(rainbow). The leucine-rich region domain is extracellular. This is where TSH will bind. The hinge region is also extracellular. Conformational changes in this region are responsible for the switch between the active vs inactive state. Finally, the transmembrane region is located within the plasma membrane. Its function is to hold the receptor into the membrane. This domain is also bound to the [https://en.wikipedia.org/wiki/G_protein G-proteins] at the N-terminus. The G-proteins are located on the intracellular side of the plasma membrane. They are important for transmitting the binding signal into the cell, setting off a protein signaling cascade.
 === Transmembrane Region===
-<scene name='95/952720/Transmembrane_region_spin/5'>The Transmembrane Region</scene> (<scene name='95/952720/Transmembrane_region_top-view/2'>top-view</scene>) is embedded within the cell membrane. Like other G-protein receptors, it is made up of a 7-pass helix <ref name="Faust"> DOI 10.1038/s41586-022-05159-1</ref>. It is made up of about 284 residues. The transmembrane region is surrounded by a "belt" of <scene name='95/952719/Tmd_cholesterol_spin/3'>15 cholesterols</scene>. When cholesterol binding sites are mutated such that they are unfunctional, TSHR activity decreases. Thus, the cholesterols are important for TSHR function <ref name="Duan"> DOI 10.1038/s41586-022-05173-3</ref>. Additionally, at the N-terminus, the transmembrane region binds to the <scene name='95/952720/Transmembrane_region_spin/4'>G-proteins</scene>, which are located intracellularly.
+<scene name='95/952720/Transmembrane_region_spin/5'>The Transmembrane Region</scene> (<scene name='95/952720/Transmembrane_region_top-view/2'>top-view</scene>) is embedded within the cell membrane. Like other G-protein receptors, it is made up of a 7-pass helix <ref name="Faust"> DOI 10.1038/s41586-022-05159-1</ref>. It is made up of about 284 residues. The transmembrane region is surrounded by a "belt" of <scene name='95/952719/Tmd_cholesterol_spin/3'>15 cholesterols</scene>. When cholesterol binding sites are mutated such that they are unfunctional, TSHR activity decreases. Thus, the cholesterols are important for TSHR function <ref name="Duan"> DOI 10.1038/s41586-022-05173-3</ref>. Additionally, at the N-terminus, the transmembrane region binds to the <scene name='95/952719/Tsh-tshr-gs_complex/2'>G-Proteins</scene>, which are located intracellularly.
 === Leucine Rich Domain===
 The <scene name='95/952719/Lrrd/1'>Leucine Rich Repeat Domain (LRRD)</scene> is part of the extracellular region of TSHR. It is made up of about 280 different residues. Connected to its C-terminus is the Hinge Region. It is made up of an extensive parallel β-sheet. This β-sheet is where TSH binds and is called the binding pocket<ref name="Duan"> DOI 10.1038/s41586-022-05173-3</ref>. The <scene name='95/952719/Binding_pocket/4'>binding pocket</scene> is a concave structure with many polar residues. This pocket is where the TSH antibody and agonist K1 bind as well as the agonist M22. These structures interact with specific residues to result in a structural change of the molecule. There is a mutation done by N-glycans at asparagine residues that plays a large role in the binding of TSH. The negative charge on these glycans contributes to the polarity of the binding pocket which mediates the binding efficiency of TSH. It has been shown that four of the five N glycan sites must be glycosylated to be in the active form<ref name="Fokina">Fokina, E.F., Shpakov, A.O. Thyroid-Stimulating Hormone Receptor: the Role in the Development of Thyroid Pathology and Its Correction. J Evol Biochem Phys 58, 1439–1454 (2022). [DOI:10.1134/S0022093022050143 https://doi.org/10.1134/S0022093022050143]</ref>.