Sandbox Reserved 1779: Difference between revisions

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===M22 Agonist and Grave's Disease===

<scene name='95/952708/M22_edited/3'>M22</scene> is a [https://en.wikipedia.org/wiki/Monoclonal_antibody monoclonal antibody] that ~~was isolated from a patient~~ with [https://www.niddk.nih.gov/health-information/endocrine-diseases/graves-disease Graves' Disease]. Grave's Disease is an autoimmune disease that is a result of hyperthyroidism, where too much TSH is being produced. This disease [https://www.niddk.nih.gov/health-information/endocrine-diseases/graves-disease effects 1 in 100 Americans and especially women or people older than 30 years of age]. The binding of <scene name='95/952708/Tsh_7t9i/1'>TSH</scene> to <scene name='95/952709/Initial_scene_with_edited_7utz/2'>TSHR</scene> results in the receptor remaining in its active conformation. In Graves' disease, autoantibodies mimic TSH function and cause thyroid overactivity. <ref name="Miguel"> doi:10.1677/JME-08-0152</ref>. The M22 [https://en.wikipedia.org/wiki/Autoantibody autoantibody] activates TSHR by causing a membrane clash with the ECD and cell membrane, keeping the TSHR in the active state by preventing the TSHR from rotating to the inactive state (Figure 3). M22 mimics TSH activation of TSHR because it is a potent activator for TSHR. <ref name="Faust"> DOI:10.1038/s41586-022-05159-1</ref> Although M22 binds in a similar manner to TSH, M22 does not interact with the hinge region when bound to TSHR, whereas TSH bound to TSHR does.<ref name="Faust"> DOI:10.1038/s41586-022-05159-1</ref> This finding shows that the hinge region is not necessary for the activation of TSHR, and leads to the discovery of other methods of activation. [[Image:Agonist pic.png|450 px|right|thumb|Figure 3: Agonist and antagonist drugs for activating or inactivating the TSHR protein. Here the membrane clashes are demonstrated on TSHR with different agonists attached. CS-17 is orange, TSH is purple, and M22 is blue in the figure. The TSHR protein is green and embedded in the protein.]]

<scene name='95/952708/M22_edited/3'>M22</scene> is a [https://en.wikipedia.org/wiki/Monoclonal_antibody monoclonal antibody] that produced by patients with [https://www.niddk.nih.gov/health-information/endocrine-diseases/graves-disease Graves' Disease]. Grave's Disease is an autoimmune disease that is a result of hyperthyroidism, where too much TSH is being produced. This disease [https://www.niddk.nih.gov/health-information/endocrine-diseases/graves-disease effects 1 in 100 Americans and especially women or people older than 30 years of age]. The binding of <scene name='95/952708/Tsh_7t9i/1'>TSH</scene> to <scene name='95/952709/Initial_scene_with_edited_7utz/2'>TSHR</scene> results in the receptor remaining in its active conformation. In Graves' disease, autoantibodies mimic TSH function and cause thyroid overactivity. <ref name="Miguel"> doi:10.1677/JME-08-0152</ref>. The M22 [https://en.wikipedia.org/wiki/Autoantibody autoantibody] activates TSHR by causing a membrane clash with the ECD and cell membrane, keeping the TSHR in the active state by preventing the TSHR from rotating to the inactive state (Figure 3). M22 mimics TSH activation of TSHR because it is a potent activator for TSHR. <ref name="Faust"> DOI:10.1038/s41586-022-05159-1</ref> Although M22 binds in a similar manner to TSH, M22 does not interact with the hinge region when bound to TSHR, whereas TSH bound to TSHR does.<ref name="Faust"> DOI:10.1038/s41586-022-05159-1</ref> This finding shows that the hinge region is not necessary for the activation of TSHR, and leads to the discovery of other methods of activation. [[Image:Agonist pic.png|450 px|right|thumb|Figure 3: Agonist and antagonist drugs for activating or inactivating the TSHR protein. Here the membrane clashes are demonstrated on TSHR with different agonists attached. CS-17 is orange, TSH is purple, and M22 is blue in the figure. The TSHR protein is green and embedded in the protein.]]

Sandbox Reserved 1779: Difference between revisions

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Revision as of 20:27, 12 April 2023 view source Jackson Langford (talk \| contribs) 162 edits No edit summary ← Older edit		Revision as of 20:36, 12 April 2023 view source Jackson Langford (talk \| contribs) 162 edits No edit summary Newer edit →
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	===M22 Agonist and Grave's Disease===		===M22 Agonist and Grave's Disease===
	<scene name='95/952708/M22_edited/3'>M22</scene> is a [https://en.wikipedia.org/wiki/Monoclonal_antibody monoclonal antibody] that ~~was isolated from a patient~~ with [https://www.niddk.nih.gov/health-information/endocrine-diseases/graves-disease Graves' Disease]. Grave's Disease is an autoimmune disease that is a result of hyperthyroidism, where too much TSH is being produced. This disease [https://www.niddk.nih.gov/health-information/endocrine-diseases/graves-disease effects 1 in 100 Americans and especially women or people older than 30 years of age]. The binding of <scene name='95/952708/Tsh_7t9i/1'>TSH</scene> to <scene name='95/952709/Initial_scene_with_edited_7utz/2'>TSHR</scene> results in the receptor remaining in its active conformation. In Graves' disease, autoantibodies mimic TSH function and cause thyroid overactivity. <ref name="Miguel"> doi:10.1677/JME-08-0152</ref>. The M22 [https://en.wikipedia.org/wiki/Autoantibody autoantibody] activates TSHR by causing a membrane clash with the ECD and cell membrane, keeping the TSHR in the active state by preventing the TSHR from rotating to the inactive state (Figure 3). M22 mimics TSH activation of TSHR because it is a potent activator for TSHR. <ref name="Faust"> DOI:10.1038/s41586-022-05159-1</ref> Although M22 binds in a similar manner to TSH, M22 does not interact with the hinge region when bound to TSHR, whereas TSH bound to TSHR does.<ref name="Faust"> DOI:10.1038/s41586-022-05159-1</ref> This finding shows that the hinge region is not necessary for the activation of TSHR, and leads to the discovery of other methods of activation. [[Image:Agonist pic.png\|450 px\|right\|thumb\|Figure 3: Agonist and antagonist drugs for activating or inactivating the TSHR protein. Here the membrane clashes are demonstrated on TSHR with different agonists attached. CS-17 is orange, TSH is purple, and M22 is blue in the figure. The TSHR protein is green and embedded in the protein.]]		<scene name='95/952708/M22_edited/3'>M22</scene> is a [https://en.wikipedia.org/wiki/Monoclonal_antibody monoclonal antibody] that produced by patients with [https://www.niddk.nih.gov/health-information/endocrine-diseases/graves-disease Graves' Disease]. Grave's Disease is an autoimmune disease that is a result of hyperthyroidism, where too much TSH is being produced. This disease [https://www.niddk.nih.gov/health-information/endocrine-diseases/graves-disease effects 1 in 100 Americans and especially women or people older than 30 years of age]. The binding of <scene name='95/952708/Tsh_7t9i/1'>TSH</scene> to <scene name='95/952709/Initial_scene_with_edited_7utz/2'>TSHR</scene> results in the receptor remaining in its active conformation. In Graves' disease, autoantibodies mimic TSH function and cause thyroid overactivity. <ref name="Miguel"> doi:10.1677/JME-08-0152</ref>. The M22 [https://en.wikipedia.org/wiki/Autoantibody autoantibody] activates TSHR by causing a membrane clash with the ECD and cell membrane, keeping the TSHR in the active state by preventing the TSHR from rotating to the inactive state (Figure 3). M22 mimics TSH activation of TSHR because it is a potent activator for TSHR. <ref name="Faust"> DOI:10.1038/s41586-022-05159-1</ref> Although M22 binds in a similar manner to TSH, M22 does not interact with the hinge region when bound to TSHR, whereas TSH bound to TSHR does.<ref name="Faust"> DOI:10.1038/s41586-022-05159-1</ref> This finding shows that the hinge region is not necessary for the activation of TSHR, and leads to the discovery of other methods of activation. [[Image:Agonist pic.png\|450 px\|right\|thumb\|Figure 3: Agonist and antagonist drugs for activating or inactivating the TSHR protein. Here the membrane clashes are demonstrated on TSHR with different agonists attached. CS-17 is orange, TSH is purple, and M22 is blue in the figure. The TSHR protein is green and embedded in the protein.]]