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Related Experiment Videos

Evolution of thyroid hormone distribution

G Schreiber1, P Prapunpoj, L Chang

  • 1Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, Victoria, Australia. g.schreiber@biochemistry.unimelb.edu.au

Clinical and Experimental Pharmacology & Physiology
|September 29, 1998
PubMed
Summary
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Transthyretin, a protein crucial for thyroid hormone transport, evolved shorter N-termini in mammals. This structural change enhanced thyroxine binding, influencing its distribution and brain accessibility during evolution.

Area of Science:

  • Biochemistry
  • Evolutionary Biology
  • Neuroscience

Background:

  • Thyroxine distribution relies on binding proteins like transthyretin (TTR).
  • TTR is unique as it's synthesized in the brain.
  • TTR synthesis timing and location vary across vertebrate evolution.

Purpose of the Study:

  • To investigate the evolutionary changes in transthyretin.
  • To understand the structural and functional adaptations of transthyretin during vertebrate evolution.
  • To explore the relationship between transthyretin N-terminus evolution and thyroxine binding affinity.

Main Methods:

  • Comparative analysis of transthyretin sequences across different vertebrate groups.
  • Phylogenetic analysis to reconstruct evolutionary history.

Related Experiment Videos

  • Structural analysis to correlate N-terminal changes with functional properties.

    • Main Results:

    • Transthyretin synthesis in the blood-brain barrier predates liver synthesis in evolution.
    • Mammalian transthyretin exhibits shorter, more hydrophilic N-termini compared to reptiles and birds.
    • Transthyretin's affinity for thyroxine increased, while its affinity for triiodothyronine decreased during eutherian evolution.
    • Evolutionary N-terminal changes are attributed to splice site shifts driven by single base mutations.

    Conclusions:

    • The evolution of transthyretin's N-terminus is linked to altered thyroxine binding and accessibility.
    • These changes likely played a role in optimizing thyroid hormone regulation during mammalian evolution.
    • Understanding transthyretin evolution provides insights into neurodevelopment and thyroid hormone function.