Sandbox Reserved 1791: Difference between revisions

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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 the extracellular TSH ligand domain. The hinge connects the Leucine Rich Repeat Domain and the Transmembrane Region. It provides flexibility for the switch between the active and inactive state of TSHR. The transmembrane region is located within the plasma membrane. Its function transmit the extracellular signal across the membrane to the intracellular [https://en.wikipedia.org/wiki/G_protein G-proteins] bound to the N-terminus of the transmembrane region<ref name="Duan"/>. Activated G-proteins then signal a robust intracellular 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 composed of a 7-pass helix <ref name="Faust"> DOI:10.1038/s41586-022-05159-1</ref>. 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, TSHR activity decreases. These cholesterols are likely important for TSHR function <ref name="Duan"/>. Additionally, at the N-terminus, the transmembrane region binds to the <scene name='95/952719/Tsh-tshr-gs_complex/3'>G-Proteins</scene>, which are located intracellularly <ref name="GOEL"/>. The G-proteins are made up of ~~three~~ subunits: α, β, γ, and Nb35. Nb35 is used to stabilize the structure by binding between the Gα and Gβ interface<ref name="Maeda"> DOI: 10.1038/s41467-018-06002-w</ref>. When TSHR is activated, it causes the Gα subunit to dissociate from the Gβγ subunits. The Gα subunit is responsible for activating [https://en.wikipedia.org/wiki/Adenylyl_cyclase adenylyl cyclase], [https://en.wikipedia.org/wiki/Phospholipase_C phospholipase C] and [https://en.wikipedia.org/wiki/Ion_channel ion channels]. This sets off the robust intracellular signaling cascade<ref name="GOEL"> PMID:24255551</ref>.

<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 composed of a 7-pass helix <ref name="Faust"> DOI:10.1038/s41586-022-05159-1</ref>. 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, TSHR activity decreases. These cholesterols are likely important for TSHR function <ref name="Duan"/>. Additionally, at the N-terminus, the transmembrane region binds to the <scene name='95/952719/Tsh-tshr-gs_complex/3'>G-Proteins</scene>, which are located intracellularly <ref name="GOEL"/>. The G-proteins are made up of four subunits: α, β, γ, and Nb35. Nb35 is used to stabilize the structure by binding between the Gα and Gβ interface<ref name="Maeda"> DOI: 10.1038/s41467-018-06002-w</ref>. When TSHR is activated, it causes the Gα subunit to dissociate from the Gβγ subunits. The Gα subunit is responsible for activating [https://en.wikipedia.org/wiki/Adenylyl_cyclase adenylyl cyclase], [https://en.wikipedia.org/wiki/Phospholipase_C phospholipase C] and [https://en.wikipedia.org/wiki/Ion_channel ion channels]. This sets off the robust intracellular signaling cascade<ref name="GOEL"> PMID:24255551</ref>.

Sandbox Reserved 1791: Difference between revisions

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@@ Line 11: / Line 11: @@
 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 the extracellular TSH ligand domain. The hinge connects the Leucine Rich Repeat Domain and the Transmembrane Region. It provides flexibility for the switch between the active and inactive state of TSHR. The transmembrane region is located within the plasma membrane. Its function transmit the extracellular signal across the membrane to the intracellular [https://en.wikipedia.org/wiki/G_protein G-proteins] bound to the N-terminus of the transmembrane region<ref name="Duan"/>. Activated G-proteins then signal a robust intracellular 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 composed of a 7-pass helix <ref name="Faust"> DOI:10.1038/s41586-022-05159-1</ref>. 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, TSHR activity decreases. These cholesterols are likely important for TSHR function <ref name="Duan"/>. Additionally, at the N-terminus, the transmembrane region binds to the <scene name='95/952719/Tsh-tshr-gs_complex/3'>G-Proteins</scene>, which are located intracellularly <ref name="GOEL"/>. The G-proteins are made up of three subunits: α, β, γ, and Nb35. Nb35 is used to stabilize the structure by binding between the Gα and Gβ interface<ref name="Maeda"> DOI: 10.1038/s41467-018-06002-w</ref>. When TSHR is activated, it causes the Gα subunit to dissociate from the Gβγ subunits. The Gα subunit is responsible for activating [https://en.wikipedia.org/wiki/Adenylyl_cyclase adenylyl cyclase], [https://en.wikipedia.org/wiki/Phospholipase_C phospholipase C] and [https://en.wikipedia.org/wiki/Ion_channel ion channels]. This sets off the robust intracellular signaling cascade<ref name="GOEL"> PMID:24255551</ref>.
+<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 composed of a 7-pass helix <ref name="Faust"> DOI:10.1038/s41586-022-05159-1</ref>. 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, TSHR activity decreases. These cholesterols are likely important for TSHR function <ref name="Duan"/>. Additionally, at the N-terminus, the transmembrane region binds to the <scene name='95/952719/Tsh-tshr-gs_complex/3'>G-Proteins</scene>, which are located intracellularly <ref name="GOEL"/>. The G-proteins are made up of four subunits: α, β, γ, and Nb35. Nb35 is used to stabilize the structure by binding between the Gα and Gβ interface<ref name="Maeda"> DOI: 10.1038/s41467-018-06002-w</ref>. When TSHR is activated, it causes the Gα subunit to dissociate from the Gβγ subunits. The Gα subunit is responsible for activating [https://en.wikipedia.org/wiki/Adenylyl_cyclase adenylyl cyclase], [https://en.wikipedia.org/wiki/Phospholipase_C phospholipase C] and [https://en.wikipedia.org/wiki/Ion_channel ion channels]. This sets off the robust intracellular signaling cascade<ref name="GOEL"> PMID:24255551</ref>.