title: Evolution of the thyroid hormone-binding protein, transthyretin.
abstract: Transthyretin (TTR) belongs to a group of proteins, which includes thyroxine-binding globulin and albumin, that bind to and transport thyroid hormones in the blood. TTR is also indirectly implicated in the carriage of vitamin A through the mediation of retinol-binding protein (RBP). It was first identified in 1942 in human serum and cerebrospinal fluid and was formerly called prealbumin for its ability to migrate faster than serum albumin on electrophoresis of whole plasma. It is a single polypeptide chain of 127 amino acids (14,000 Da) and is present in the plasma as a tetramer of noncovalently bound monomers. The major sites of synthesis of TTR in eutherian mammals, marsupials, and birds are the liver and choroid plexus but in reptiles it is synthesised only in the choroid plexus. The observation that TTR is strongly expressed in the choroid plexus but not in the liver of the stumpy-tailed lizard and the strong conservation of expression in the choroid plexus from reptiles to mammals have been taken as evidence to suggest that extrahepatic synthesis of TTR evolved first. The identification and cloning of TTR from the liver of an amphibian, Rana catesbeiana, and a teleost fish, Sparus aurata, and its absence from the choroid plexus of both species suggest an alternative model for its evolution. Protein modelling studies are presented that demonstrate differences in the electrostatic characteristics of the molecule in human, rat, chicken, and fish, which may explain why, in contrast to TTR from human and rat, TTR from fish and birds preferentially binds triiodo-l-thyronine.
authors.affiliation: Centro de Ciências de MAR (CCMAR), Universidade do Algarve, Campus de Gambelas, 8000 Faro, Portugal.
authors.forename: D M
authors.initials: DM
authors.lastname: Power
authors.forename: N P
authors.initials: NP
authors.lastname: Elias
authors.forename: S J
authors.initials: SJ
authors.lastname: Richardson
authors.forename: J
authors.initials: J
authors.lastname: Mendes
authors.forename: C M
authors.initials: CM
authors.lastname: Soares
authors.forename: C R
authors.initials: CR
authors.lastname: Santos
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018076:DNA, Complementary / Q000737:chemistry; D019143:Evolution, Molecular; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010802:Phylogeny; D011228:Prealbumin / Q000737:chemistry / Q000235:genetics*; D017385:Sequence Homology
chemical_list: D018076:DNA, Complementary; D011228:Prealbumin