The Evolution of the Thyroid Hormone Distributor Protein Transthyretin in the Order Insectivora, Class Mammalia

Prapunpoj, Porntip; Richardson, Samantha; Fumagalli, Luca; Schreiber, Gerhard

doi:10.1093/oxfordjournals.molbev.a026403

Cited by 23 publications

(22 citation statements)

References 42 publications

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“…A maximum parsimony analysis was performed with the amino acid sequences of known TTR genes (Prapunpoj et al 2000a). Such an analysis shows a monophyletic tree for TTR (Fig.…”

Section: Evolution Of the Tissue Pattern Of Ttr Gene Expressionmentioning

confidence: 99%

“…There is negative cooperativity between the two sites (Ferguson et al 1975, Neumann et al 2001. The best conserved regions of the polypeptide chain are the binding site and the amino acids lining the channel , Prapunpoj et al 2000a. It is only relatively recently that data became available for the three-dimensional structure of the first 10 amino acids from the N-termini of human TTR.…”

Section: Selection Pressure Involved In Ttr Evolution Relationship Bmentioning

confidence: 99%

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The evolutionary and integrative roles of transthyretin in thyroid hormone homeostasis

Schreiber

2002

Journal of Endocrinology

132

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In larger mammals, thyroid hormone-binding plasma proteins are albumin, transthyretin (TTR) and thyroxine (T4)-binding globulin. They differ characteristically in affinities and release rates for T4 and triiodothyronine (T3). Together, they form a 'buffering' system counteracting thyroid hormone permeation from aqueous to lipid phases. Evolution led to important differences in the expression pattern of these three proteins in tissues. In adult liver, TTR is only made in eutherians and herbivorous marsupials. During development, it is also made in tadpole and fish liver. More intense TTR synthesis than in liver is found in the choroid plexus of reptilians, birds and mammals, but none in the choroid plexus of amphibians and fish, i.e. species without a neocortex. All brainmade TTR is secreted into the cerebrospinal fluid, where it becomes the major thyroid hormone-binding protein.During ontogeny, the maximum TTR synthesis in the choroid plexus precedes that of the growth rate of the brain and occurs during the period of maximum neuroblast replication. TTR is only one component in a network of factors determining thyroid hormone distribution. This explains why, under laboratory conditions, TTR-knockout mice show no major abnormalities. The ratio of TTR affinity for T4 over affinity for T3 is higher in eutherians than in reptiles and birds. This favors T4 transport from blood to brain providing more substrate for conversion of the biologically less active T4 into the biologically more active T3 by the tissue-specific brain deiodinases. The change in affinity of TTR during evolution involves a shortening and an increase in the hydrophilicity of the N-terminal regions of the TTR subunits. The molecular mechanism for this change is a stepwise shift of the splice site at the intron 1/exon 2 border of the TTR gene. The shift probably results from a sequence of single base mutations. Thus, TTR evolution provides an example for a molecular mechanism of positive Darwinian evolution. The amino acid sequences of fish and amphibian TTRs are very similar to those in mammals, suggesting that substantial TTR evolution occurred before the vertebrate stage. Open reading frames for TTR-like sequences already exist in Caenorhabditis elegans, yeast and Escherichia coli genomes.

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“…A maximum parsimony analysis was performed with the amino acid sequences of known TTR genes (Prapunpoj et al 2000a). Such an analysis shows a monophyletic tree for TTR (Fig.…”

Section: Evolution Of the Tissue Pattern Of Ttr Gene Expressionmentioning

confidence: 99%

Section: Selection Pressure Involved In Ttr Evolution Relationship Bmentioning

confidence: 99%

The evolutionary and integrative roles of transthyretin in thyroid hormone homeostasis

Schreiber

2002

Journal of Endocrinology

132

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“…TTR was found in serum from all studied species of birds and eutherians (5,8,9,10,15,17,25,26), which are known homeotherms. TTR was found in serum from all studied species of birds and eutherians (5,8,9,10,15,17,25,26), which are known homeotherms.…”

Section: Hypothesis 2 Onset Of Hepatic Ttr Synthesis Is Related To Hmentioning

confidence: 95%

“…A phylogenetic tree built using a maximum parsimony algorithm was built using TTR amino acid sequences, residues 10 to 127 (numbering for human TTR) (17). The sea bream TTR amino acid sequence was used as the out-group.…”

Section: Evolution Of the Primary Structure Of Ttrmentioning

confidence: 99%

The Evolution of Transthyretin Synthesis in Vertebrate Liver, in Primitive Eukaryotes and in Bacteria

Richardson¹

2002

Clinical Chemistry and Laboratory Medicine

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Thyroid hormones are evolutionarily old signal molecules, which can partition between compartments by partitioning into lipid membranes. The role of thyroid hormone distributor proteins is to ensure that sufficient thyroid hormone remains in the bloodstream. Of particular interest is the role of transthyretin, synthesised by the liver and secreted into the blood. In this review, three hypotheses are presented, suggesting the selection pressures leading to the onset of transthyretin synthesis in the liver during evolution. A thyroid hormone distribution network would be a selection advantage over a single protein performing this function. Similarly to the situation in eutherians, hepatic transthyretin synthesis in marsupials is under negative acute phase regulation. The overall three-dimensional structure of transthyretin did not change appreciably during vertebrate evolution. The region of the primary sequence which evolved most was the N-terminal region of the subunit. The N-termini of transthyretin changed from longer and more hydrophobic in reptiles/birds, to shorter and more hydrophilic in eutherians. These changes are correlated with a change in preference from binding of triiodothyronine, to binding thyroxine. As the rest of the molecule had not changed significantly during vertebrate evolution, the gene coding for transthyretin must have evolved prior to the divergence of the vertebrates from the non-vertebrates. Five open reading frames in the genomes of C. elegans (2), S. dublin, S. pombe and E. coli were identified. The protein products are predicted to form tetramers similar to transthyretins. Two possible functions of these proteins are suggested.

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“…During the evolution of vertebrates, the amino acid sequence in the central domain of TTR monomer was highly conserved. The predominant changes were in the N‐terminal region, with smaller changes in the C‐terminal region of the TTR subunit . The N‐terminal sequences of birds, reptiles, amphibians and fish are longer or relatively more hydrophobic than those of mammalian TTRs.…”

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confidence: 98%

Increasing the length and hydrophobicity of the C‐terminal sequence of transthyretin strengthens its binding affinity to retinol binding protein

et al. 2017

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Transthyretin ( TTR ) is a transporter for thyroid hormone ( TH ) and retinol, the latter via binding with retinol binding protein ( RBP ). Both the N‐terminal and C‐terminal regions of the TTR subunit are located in close proximity to the central binding channel for ligands. During the evolution of vertebrates, these regions changed in length and hydropathy. The changes in the N‐terminal sequence were demonstrated to affect the binding affinities for TH s and RBP . Here, the effects of changes in the C‐terminal sequence were determined. Three chimeric TTR s, namely pigC/hu TTR (human TTR with the C‐terminal sequence changed to that of Sus scrofa TTR ), xenoN/pigC/hu TTR (human TTR with the N‐terminal and C‐terminal sequences changed to those of Xenopus laevis and S. scrofa , respectively), and pigC/croc TTR ( Crocodylus porosus TTR with the C‐terminal sequence changed to that of S. scrofa TTR ), were constructed and their binding affinities for human RBP were determined at low TTR / RBP molar ratio using chemiluminescence immunoblotting. The binding dissociation constant ( K d ) values of pigC/hu TTR , xenoN/pigC/hu TTR and pigC/croc TTR were 3.20 ± 0.35, 1.53 ± 0.38 and 0.31 ± 0.04 μ m , respectively, and the K d values of human and C. porosus TTR were 4.92 ± 0.68 and 1.42 ± 0.45 μ m , respectively. These results demonstrate chimeric TTR s bound RBP with a higher strength than wild‐type TTR s, and the changes in the C‐terminal sequence of TTR had a positive effect on its binding affinity for RBP . In addition, changes to the N‐terminal and C‐terminal sequences showed comparable effects on the binding affinity.

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The Evolution of the Thyroid Hormone Distributor Protein Transthyretin in the Order Insectivora, Class Mammalia

Cited by 23 publications

References 42 publications

The evolutionary and integrative roles of transthyretin in thyroid hormone homeostasis

The evolutionary and integrative roles of transthyretin in thyroid hormone homeostasis

The Evolution of Transthyretin Synthesis in Vertebrate Liver, in Primitive Eukaryotes and in Bacteria

Increasing the length and hydrophobicity of the C‐terminal sequence of transthyretin strengthens its binding affinity to retinol binding protein

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