Sandbox Reserved 1792: Difference between revisions

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== Introduction ==
== Introduction ==
[[Image:Thyroid System.png|300 px|right|thumb| Fig.1 An overview of the Thyroid System source: [https://en.wikipedia.org/wiki/Thyroid_hormones Thyroid Hormones]]]
[[Image:Thyroid System.png|300 px|right|thumb| Fig.1 An overview of the Thyroid System source: [https://en.wikipedia.org/wiki/Thyroid_hormones Thyroid Hormones]]]
'''Thyroid Stimulating Hormone Receptor (TSHR)''' is a type of [https://proteopedia.org/wiki/index.php/GPCRs G-Protein Coupled Receptor (GPCR)] found in human thyroid follicles. It is activated by the [https://en.wikipedia.org/wiki/Thyroid-stimulating_hormone Thyroid Stimulating Hormone (TSH)] which is known as thyrotropin. Activation of TSHR is neccessary for activating a signaling pathway for the production of thyroid hormones such as [https://en.wikipedia.org/wiki/Triiodothyronine T<sub>3</sub>] and [https://en.wikipedia.org/wiki/Thyroid_hormones T<sub>4</sub>] (Fig 1).  
'''Thyroid Stimulating Hormone Receptor (TSHR)''' is a [https://proteopedia.org/wiki/index.php/GPCRs G-Protein Coupled Receptor (GPCR)] found in human thyroid follicles. TSHR is activated by the [https://en.wikipedia.org/wiki/Thyroid-stimulating_hormone Thyroid Stimulating Hormone (TSH)] also known as thyrotropin. Activation of TSHR is initiates a signaling pathway for the production of thyroid hormones such as [https://en.wikipedia.org/wiki/Triiodothyronine T<sub>3</sub>] and [https://en.wikipedia.org/wiki/Thyroid_hormones T<sub>4</sub>] (Fig 1).  
== Structure==
== Structure==
TSHR forms a complex with TSH and G<sub>s</sub> proteins. This is called the <scene name=scene name='95/952720/Tsh-tshr-gs_complex/3'>TSH-TSHR-Gs Complex</scene>.  
TSHR forms an active signalling complex with TSH and G<sub>s</sub> proteins. This is called the <scene name=scene name='95/952720/Tsh-tshr-gs_complex/3'>TSH-TSHR-Gs Complex</scene>. TSH contains an α and a β subunit. The α subunit is a shared subunit amongst glycoproteins. The β subunit is unique to TSH. TSH binds to the extracellular domain of TSHR. 
<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.
<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 intracellular. The G-protein is made up of three subunits: α,β, and γ. 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 TSH signaling pathway.
=== Transmembrane Region===
=== 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='95/952720/Tmd_cholesterol_spin/2'>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='95/952720/Tmd_cholesterol_spin/2'>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.  
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