{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T05:00:40Z","timestamp":1768539640057,"version":"3.49.0"},"reference-count":46,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2014,10,14]],"date-time":"2014-10-14T00:00:00Z","timestamp":1413244800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2015,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Transthyretin (<jats:styled-content style=\"fixed-case\">TTR<\/jats:styled-content>) is a visceral protein, which facilitates the transport of thyroid hormones in blood and cerebrospinal fluid. The homotetrameric structure of <jats:styled-content style=\"fixed-case\">TTR<\/jats:styled-content> enables the simultaneous binding of two thyroid hormones per molecule. Each <jats:styled-content style=\"fixed-case\">TTR<\/jats:styled-content> subunit provides a single cysteine residue (Cys<jats:sub>10<\/jats:sub>), which is frequently affected by oxidative post\u2010translational modifications. As Cys<jats:sub>10<\/jats:sub> is part of the thyroid hormone\u2010binding channel within the <jats:styled-content style=\"fixed-case\">TTR<\/jats:styled-content> molecule, <jats:styled-content style=\"fixed-case\">PTM<\/jats:styled-content> of Cys<jats:sub>10<\/jats:sub> may influence the binding of thyroid hormones. Therefore, we analysed the effects of Cys<jats:sub>10<\/jats:sub> modification with sulphonic acid, cysteine, cysteinylglycine and glutathione on binding of triiodothyronine (T3) by molecular modelling. Furthermore, we determined the <jats:styled-content style=\"fixed-case\">PTM<\/jats:styled-content> pattern of <jats:styled-content style=\"fixed-case\">TTR<\/jats:styled-content> in serum of patients with thyroid disease by immunoprecipitation and mass spectrometry to evaluate this association <jats:italic>in vivo<\/jats:italic>. The <jats:italic>in silico<\/jats:italic> assays demonstrated that oxidative <jats:styled-content style=\"fixed-case\">PTM<\/jats:styled-content> of <jats:styled-content style=\"fixed-case\">TTR<\/jats:styled-content> resulted in substantial reorganization of the intramolecular interactions and also affected the binding of T3 in a chemotype\u2010 and site\u2010specific manner with S\u2010glutathionylation as the most potent modulator of T3 binding. These findings were supported by the <jats:italic>in vivo<\/jats:italic> results, which indicated thyroid function\u2010specific patterns of <jats:styled-content style=\"fixed-case\">TTR<\/jats:styled-content> with a substantial decrease in S\u2010sulphonated, S\u2010cysteinylglycinated and S\u2010glutathionylated <jats:styled-content style=\"fixed-case\">TTR<\/jats:styled-content> in hypothyroid patients. In conclusion, this study provides evidence that oxidative modifications of Cys<jats:sub>10<\/jats:sub> seem to affect binding of T3 to <jats:styled-content style=\"fixed-case\">TTR<\/jats:styled-content> probably because of the introduction of a sterical hindrance and induction of conformational changes. As oxidative modifications can be dynamically regulated, this may represent a sensitive mechanism to adjust thyroid hormone availability.<\/jats:p>","DOI":"10.1111\/jcmm.12446","type":"journal-article","created":{"date-parts":[[2014,10,14]],"date-time":"2014-10-14T08:51:38Z","timestamp":1413276698000},"page":"359-370","source":"Crossref","is-referenced-by-count":26,"title":["Post\u2010translational modifications of transthyretin affect the triiodonine\u2010binding potential"],"prefix":"10.1111","volume":"19","author":[{"given":"Andrea","family":"Henze","sequence":"first","affiliation":[{"name":"Institute of Nutrition University of Potsdam Nuthetal Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Homann","sequence":"additional","affiliation":[{"name":"Institute of Nutrition University of Potsdam Nuthetal 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