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Updated: Jun 20, 2026

Demonstration of the Sequence Alignment to Predict Across Species Susceptibility Tool for Rapid Assessment of Protein Conservation
Published on: February 10, 2023
Evolutionary changes to transthyretin: structure and function of a transthyretin-like ancestral protein
1Department of Biochemistry and Molecular Biology, Bio21 Institute, The University of Melbourne, Victoria, Australia. sarah.hennebry@bakeridi.edu.au
Abstract:
The structure of the thyroid hormone distributor protein, transthyretin, has been highly conserved during the evolution of vertebrates. Over the last decade, studies into the evolution of transthyretin have revealed the existence of a transthyretin homolog, transthyretin-like protein, in all kingdoms. Phylogenetic studies have suggested that the transthyretin gene in fact arose as a result of a duplication of the transthyretin-like protein gene in early protochordate evolution. Structural studies of transthyretin-like proteins from various organisms have revealed the remarkable conservation of the transthyretin-like protein/transthyretin fold. The only significant differences between the structures of transthyretin-like protein and transthyretin were localized to the dimer-dimer interface and indicated that thyroid hormones could not be bound by transthyretin-like protein. All transthyretin-like proteins studied to date have been demonstrated to function in purine metabolism by hydrolysing the oxidative product of uric acid, 5-hydroxyisourate. The residues characterizing the catalytic site in transthyretin-like proteins are 100% conserved in all transthyretin-like protein sequences but are absent in transthyretins. Therefore, it was proposed that following duplication of the transthyretin-like protein gene, loss of these catalytic residues resulted in the formation of a deep, negatively charged channel that runs through the centre of the transthyretin tetramer. The results thus demonstrate the remarkable evolution of the transthyretin-like protein/transthyretin protein from a hydrolytic enzyme to a thyroid hormone distributor protein.
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