Evolution of the Thyroid Hormone Distributor Protein Transthyretin in Microbes, <i>C. elegans</i>, and Vertebrates

Abstract

Transthyretin (TTR) is an extracellular thyroid hormone distributor protein in vertebrates, whose structure has been highly conserved between fish and humans. However, the ligand preferentially bound by TTR has changed during evolution from 3',3,5-L-triiodothyronine (T3) to 3',5',3,5-l-tetraiodothyronine (T4). We identified genes in the genomes of >50 species of nonvertebrates, which could code for TTR-like proteins. Molecular modeling suggested most would have similar 3D structures and electrostatic surface potentials to vertebrate TTRs. We amplified TTR-like genes from a C. elegans cDNA library, demonstrating that it is transcribed. We synthesized recombinant TTR-like proteins from S. dublin and C. elegans. These proteins form tetramers similarly to vertebrate TTRs, but their ligands remain elusive.