Evolution of the Thyroid Hormone-Binding Protein, Transthyretin

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 ide...

Full description

Saved in:
Bibliographic Details
Published in:General and Comparative Endocrinology 2000-09, Vol.119 (3), p.241-255
Main Authors: Power, D.M., Elias, N.P., Richardson, S.J., Mendes, J., Soares, C.M., Santos, C.R.A.
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
distribution and function
DNA, Complementary - chemistry
evolution
Evolution, Molecular
Humans
Models, Molecular
Molecular Sequence Data
Molecular Structure
Phylogeny
Prealbumin - chemistry
Prealbumin - genetics
Sequence Homology
structure
thyroid hormones
transthyretin
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0016-6480
1095-6840
DOI:10.1006/gcen.2000.7520