Chromium(III) ion and thyroxine cooperate to stabilize the transthyretin tetramer and suppress in vitro amyloid fibril formation

Transthyretin (TTR) amyloid fibril formation, which is triggered by the dissociation of tetrameric TTR, appears to be the causative factor in familial amyloidotic polyneuropathy and senile systemic amyloidosis. Binding of thyroxine (T4), a native ligand of TTR, stabilizes the tetramer, but the bioavailability of T4 for TTR binding is limited due to the preferential binding of T4 to globulin, the major T4 carrier in plasma. Here, we show that Cr3+ increased the T4-binding capacity of wild-type (WT) and amyloidogenic V30M-TTR. Moreover, we demonstrate that Cr3+ and T4 cooperatively suppressed in vitro fibril formation due to the stabilization of WT-TTR and V30M-TTR.