Evolutionary changes to transthyretin: structure-function relationships

Transthyretin is one of the three major thyroid hormone-binding proteins in plasma and/or cerebrospinal fluid of vertebrates. It transports retinol via binding to retinol-binding protein, and exists mainly as a homotetrameric protein of similar to 55 kDa in plasma. The first 3D structure of transthyretin was an X-ray crystal structure from human transthyretin. Elucidation of the structure-function relationship of transthyretin has been of significant interest since its highly conserved structure was shown to be associated with several aspects of metabolism and with human diseases such as amyloidosis. Transthyretin null mice do not have an overt phenotype, probably because transthyretin is part of a network with other thyroid hormone distributor proteins. Systematic study of the evolutionary changes of transthyretin structure is an effective way to elucidate its function. This review summarizes current knowledge about the evolution of structural and functional characteristics of vertebrate transthyretins. The molecular mechanism of evolutionary change and the resultant effects on the function of transthyretin are discussed.