Sandbox Reserved 1791: Difference between revisions
From Proteopedia
Jump to navigationJump to search
No edit summary |
No edit summary |
||
| Line 17: | Line 17: | ||
<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/4'>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, and γ. Nb35 a fourth subunit that stabilizes 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/4'>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, and γ. Nb35 a fourth subunit that stabilizes 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>. | ||
== Antibodies == | == Antibodies == | ||
[https://my.clevelandclinic.org/health/body/22971-antibodies Antibodies] are | [https://my.clevelandclinic.org/health/body/22971-antibodies Antibodies] are important for the thyroid response to regulate the metabolism. These proteins are made from an immune system response to get rid of unwanted antigens in the body. [https://www.btf-thyroid.org/thyroid-antibodies-explained Thyroid antibodies] are made when the body attacks the thyroid tissues. These antibodies are made to mimic [https://my.clevelandclinic.org/health/articles/23524-thyroid-stimulating-hormone-tsh-levels TSH (Thyroid Stimulating Hormone)]. TSH is released from the pituitary gland to bind to TSHR and stimulate the thyroid to make T3 and T4 hormones to regulate the metabolism. These thyroid antibodies bind to the concave surface of the LRRD. | ||
=== M22 and K1 === | === M22 and K1 === | ||
M22 is an activating antibody for [https://en.wikipedia.org/wiki/Thyrotropin_receptor TSHR]. This antibody mimics [https://my.clevelandclinic.org/health/articles/23524-thyroid-stimulating-hormone-tsh-levels TSH] to activate the thyroid gland to produce [https://www.healthyandnaturalworld.com/t3-t4-thyroid-hormones/ T3 and T4 hormones]. M22 makes a stronger interaction with TSHR than TSH does due to a larger number of hydrogen bonds (14 H bonds for M22 and 3 for TSH) and salt bridge interactions with the concave surface of the LRRD<ref name="M22"> DOI 10.1677/JME-08-0152</ref>. This interaction is key for understanding why M22 activates TSHR and does not release TSHR to go into the inactive state even when T3 and T4 levels are high<ref name="M22"> DOI 10.1677/JME-08-0152</ref>. | M22 is an activating antibody for [https://en.wikipedia.org/wiki/Thyrotropin_receptor TSHR]. This antibody mimics [https://my.clevelandclinic.org/health/articles/23524-thyroid-stimulating-hormone-tsh-levels TSH] to activate the thyroid gland to produce [https://www.healthyandnaturalworld.com/t3-t4-thyroid-hormones/ T3 and T4 hormones]. M22 makes a stronger interaction with TSHR than TSH does due to a larger number of hydrogen bonds (14 H bonds for M22 and 3 for TSH) and salt bridge interactions with the concave surface of the LRRD<ref name="M22"> DOI 10.1677/JME-08-0152</ref>. This interaction is key for understanding why M22 activates TSHR and does not release TSHR to go into the inactive state even when T3 and T4 levels are high<ref name="M22"> DOI 10.1677/JME-08-0152</ref>. | ||
