Transthyretin (TTR) is a thyroid hormone-binding protein that transports thyroxine from the bloodstream into the brain. It can easily be detected in both serum and cerebrospinal fluid. TTR is highly expressed in choroid plexus epithelial cells, retina pigment epithelium and liver. Tetramer dissociation and partial unfolding leads to the formation of aggregates and amyloid fibrils. Small molecules that occupy at least one of the thyroid hormone binding sites stabilize the tetramer, thereby stabilizing the native state and protecting against misfolding and the formation of amyloid fibrils. Less than 1% of plasma prealbumin molecules are normally involved in thyroxine transport. L-thyroxine binds by an order of magnitude stronger to transthyretin than does the triiodo-L-thyronine. Thyroxine-binding globulin is the major carrier protein for thyroid hormones. About 40% of plasma transthyretin circulates in a tight protein-protein complex with the plasma retinol-binding protein (RBP). The formation of the complex with RBP stabilizes the binding of retinol to RBP and decreases the glomerular filtration and renal catabolism of the relatively small RBP molecule. There is evidence for two binding sites for RBP, one possibly being a region that includes Ile-104, located on the outer surface of the transthyretin molecule.
Swiss-Prot Accession Number: P02766