Transthyretin (TTR) is a visceral protein, which facilitates the transport of 
thyroid hormones in blood and cerebrospinal fluid. The homotetrameric structure 
of TTR enables the simultaneous binding of two thyroid hormones per molecule. 
Each TTR subunit provides a single cysteine residue (Cys10 ), which is 
frequently affected by oxidative post-translational modifications. As Cys10 is 
part of the thyroid hormone-binding channel within the TTR molecule, PTM of 
Cys10 may influence the binding of thyroid hormones. Therefore, we analysed the 
effects of Cys10 modification with sulphonic acid, cysteine, cysteinylglycine 
and glutathione on binding of triiodothyronine (T3) by molecular modelling. 
Furthermore, we determined the PTM pattern of TTR in serum of patients with 
thyroid disease by immunoprecipitation and mass spectrometry to evaluate this 
association in vivo. The in silico assays demonstrated that oxidative PTM of TTR 
resulted in substantial reorganization of the intramolecular interactions and 
also affected the binding of T3 in a chemotype- and site-specific manner with 
S-glutathionylation as the most potent modulator of T3 binding. These findings 
were supported by the in vivo results, which indicated thyroid function-specific 
patterns of TTR with a substantial decrease in S-sulphonated, 
S-cysteinylglycinated and S-glutathionylated TTR in hypothyroid patients. In 
conclusion, this study provides evidence that oxidative modifications of Cys10 
seem to affect binding of T3 to TTR 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.