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Related Experiment Videos

Crocodile transthyretin: structure, function, and evolution.

Porntip Prapunpoj1, Samantha J Richardson, Gerhard Schreiber

  • 1Department of Biochemistry, Faculty of Science, Prince of Songkla University, Hat-Yai, Songkhla 90112, Thailand. pporntip@ratree.psu.ac.th

American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
|September 14, 2002
PubMed
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The study reveals that the N-terminal region of crocodile transthyretin (TTR) influences thyroid hormone binding, offering insights into TTR evolution. This structural variation highlights positive Darwinian evolution in vertebrate TTRs.

Area of Science:

  • Evolutionary biology
  • Molecular biology
  • Biochemistry

Background:

  • Transthyretin (TTR) plays a crucial role in thyroid hormone transport and is a valuable model for studying protein evolution.
  • Understanding TTR evolution across different vertebrate classes provides insights into molecular adaptation and speciation.

Purpose of the Study:

  • To investigate the structure and function of Crocodylus porosus transthyretin (crocTTR) as a key intermediate in TTR evolution.
  • To elucidate the role of the N-terminal region in modulating thyroid hormone binding affinity.

Main Methods:

  • Cloning and sequencing of crocTTR cDNA to deduce its amino acid sequence.
  • Synthesis of recombinant crocTTR and chimeric TTR constructs using the yeast Pichia pastoris.
  • Analysis of thyroid hormone (T4 and T3) binding affinities to wild-type and chimeric TTRs.

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Main Results:

  • CrocTTR possesses a long, hydrophobic N-terminal region, distinct from mammalian TTRs but similar to avian and lizard TTRs.
  • CrocTTR exhibits higher affinity for triiodothyronine (T3) than thyroxine (T4), differing from mammalian TTRs.
  • The N-terminal region was identified as a key modulator of T4 and T3 binding characteristics, with structural variations attributed to splice site shifts.

Conclusions:

  • The N-terminal region of TTR significantly influences thyroid hormone binding properties, demonstrating functional adaptation during evolution.
  • The evolution of TTR, as exemplified by crocTTR, showcases positive Darwinian evolution and its underlying molecular mechanisms.
  • Comparative analysis of vertebrate TTRs reveals conserved and divergent structural features driving functional diversification.