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From Proteopedia

Thyroid Stimulating Hormone Receptor (TSHR)

spinqualitylabelsall models The Human Thyroid Stimulating Hormone Receptor Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image This is a default text for your page '. Click above on edit this page' to modify. Be careful with the < and > signs. You may include any references to papers as in: the use of JSmol in Proteopedia [1] or to the article describing Jmol [2] to the rescue. Introduction Thyroid Stimulating Hormone Receptor (TSHR) is a type of G-Protein Coupled Receptor (GPCR) found in human thyroid follicles. It is activated by the 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 T3 and T4 An overview of the Thyroid System source: Thyroid Hormones Structure TSHR forms a complex with TSH and Gs proteins. This is called the . : Leucine Rich Region Domain (coral), the hinge region (blue-purple), and the transmembrane region. The (rainbow). The leucine rich region domain is located on the outside of the cell. 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 G-proteins. Transmembrane Region The () is embedded within the cell membrane. Like other G-proteins, it is made up of a 7-pass helix [3]

References

1. ↑ Hanson, R. M., Prilusky, J., Renjian, Z., Nakane, T. and Sussman, J. L. (2013), JSmol and the Next-Generation Web-Based Representation of 3D Molecular Structure as Applied to Proteopedia. Isr. J. Chem., 53:207-216. doi:http://dx.doi.org/10.1002/ijch.201300024
2. ↑ Herraez A. Biomolecules in the computer: Jmol to the rescue. Biochem Mol Biol Educ. 2006 Jul;34(4):255-61. doi: 10.1002/bmb.2006.494034042644. PMID:21638687 doi:10.1002/bmb.2006.494034042644
3. ↑

   Hinge Region

   The (purple-blue) connects the Transmembrane Region to the Leucine Rich Domain. It is made up of two <math>α</math>-helices that are connected via di-sulfide bonds. Interactions between these two helices and TSH help orient TSH properly. These interactions are essential for TSH binding, however, they are not required for the activation of TSHR. Conformational changes in this region, specifically the orientation of Y279 (greenlink), are responsible for the bringing TSHR into the active state <ref> === Leucine Rich Domain=== <scene name='95/952720/Lrrd/1'>LRRD</scene> === Binding Pocket===

   == Active vs Inactive State== When TSHR is not bound to TSH, it is in the inactive state. This is also considered the "down" state because the LRRD is pointing down. When TSH binds to TSHR, interactions between TSH and the cell-membrane cause TSHR to take on the active or "up" state. During this transition, the Extracellular domains rotate 55° along an axis. This rotation is caused by conformational changes within the hinge region ('''green link'''), specifically at the Y279 residue. This residue moves 6 angstroms relative to I486, which is a residue located in the Transmembrane Region <ref name=”Faust”> == Specific Residues ==

   == Biological Relevance == This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

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