{"id":1288,"date":"2026-01-24T08:35:20","date_gmt":"2026-01-24T08:35:20","guid":{"rendered":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/2026\/01\/24\/molecular-mimicry-between-thyroid-stimulating-auoantibody-and-tsh-binding-to-the-tsh-receptor\/"},"modified":"2026-01-24T08:35:20","modified_gmt":"2026-01-24T08:35:20","slug":"molecular-mimicry-between-thyroid-stimulating-auoantibody-and-tsh-binding-to-the-tsh-receptor","status":"publish","type":"post","link":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/2026\/01\/24\/molecular-mimicry-between-thyroid-stimulating-auoantibody-and-tsh-binding-to-the-tsh-receptor\/","title":{"rendered":"MOLECULAR MIMICRY BETWEEN THYROID STIMULATING AUOANTIBODY AND TSH BINDING TO THE TSH RECEPTOR"},"content":{"rendered":"
Nunez Miguel R.1, 2<\/sup>, Chirgadze D. Y.2<\/sup>, Sanders J.1<\/sup>, Blundell T. L.2<\/sup>, Furmaniak J.1<\/sup>, Rees Smith B.1<\/sup><\/div>\n
1<\/sup>FIRS Laboratories, RSR Ltd, Parc Ty Glas, Llanishen, Cardiff, UK; 2<\/sup>Department of Biochemistry, University of Cambridge, Cambridge, UK<\/div>\n
\n

Abstract<\/h2>\n

Autoantibodies in sera from patients with Graves’ disease mimic TSH binding to the TSH receptor (TSHR) and TSH biological activity. Recently a crystal structure of the human thyroid stimulating autoantibody (M22) bound to the TSHR leucine rich domain (LRD) has been solved and provides opportunities to study the interactions between M22 and the TSHR in detail. In addition a new comparative model of the TSH-TSHR LRD complex has been built based on the crystal structures of the M22-TSHR LRD and the FSH-FSHR LRD complexes.
Electrostatic interactions, hydrogen bonds and van der Waals interactions produced by M22 with the TSHR LRD in the crystal structure of the M22-TSHR LRD complex and the interactions produced by TSH with the TSHR LRD in our latest comparative model of the TSH-TSHR LRD have been studied and compared.
The results indicate that M22 light chain (LC) interactions with the LRD mimic the interactions between the TSH β chain and the LRD. Both, M22 LC and TSH β chain interact predominantly with the N- and the C-terminal ends of the concave face of the LRD in contrast, M22 heavy chain (HC) and TSH α chain interact mostly with the central part of the concave face of the LRD. Out of the interactions that are similar between the two complexes, in most cases, M22 HC and TSH α chain interact with the same TSHR residues and M22 LC and TSH β chain interact with the same TSHR residues, respectively. Furthermore, M22 and TSH show similarities in their electrostatic surface potential in the areas that interact with the TSHR LRD. In particular, two areas on the surface of M22 show similar charge distributions as two areas on the surface of TSH. For example, negatively charged TSH? D91 and M22LC D52 interact with positively charged TSHR R109. Also positively charged TSH? R76 and M22 HC R28 both interact with negatively charged TSHR D151.
Overall therefore, M22 LC mimics TSH ? and M22 HC mimics TSH ? in binding to the receptor and our studies provide a detailed insight into how thyroid stimulating autoantibodies mimic TSH binding. This should help to unravel the mechanisms of TSHR activation and provide opportunities for developing improved therapeutics for control of TSHR activation in Graves’ disease.<\/div>\n","protected":false},"excerpt":{"rendered":"

Nunez Miguel R.1, 2, Chirgadze D. Y.2, Sanders J.1, Blundell T. L.2, Furmaniak J.1, Rees Smith B.1 1FIRS Laboratories, RSR Ltd, Parc Ty Glas, Llanishen, Cardiff, UK; 2Department of Biochemistry, University of Cambridge, Cambridge, UK Abstract Autoantibodies in sera from patients with Graves’ disease mimic TSH binding to the TSH receptor (TSHR) and TSH biological Read More<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[45,2,9],"tags":[],"class_list":["post-1288","post","type-post","status-publish","format-standard","hentry","category-volume-7-issue-3","category-journal-articles","category-volume-7"],"_links":{"self":[{"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/posts\/1288","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/comments?post=1288"}],"version-history":[{"count":0,"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/posts\/1288\/revisions"}],"wp:attachment":[{"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/media?parent=1288"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/categories?post=1288"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/tags?post=1288"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}