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Deiodinases share an evolutionarily conserved thyroid hormone-binding motif.

Salvatore Benvenga1, Fabrizio Guarneri2

  • 1Department of Clinical and Experimental Medicine - Endocrinology, University of Messina, via Consolare Valeria - Gazzi, 98125 Messina, Italy.

Frontiers in Bioscience (Landmark Edition)
|May 18, 2018
PubMed
Summary

A shared thyroid hormone (TH) binding motif exists across plasma carriers, cell transporters, nuclear receptors, and deiodinases. This conserved domain, likely from an ancestral gene, explains diverse protein interactions with TH.

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Endocrinology

Background:

  • Thyroid hormone (TH) interacts with various proteins including plasma carriers (THPC), cell surface transporters (CSTT), and nuclear receptors (TR).
  • A conserved 49-position motif for TH binding has been identified in these proteins.
  • Selenodeiodinases (dio-1, dio-2, dio-3) are crucial enzymes in TH metabolism.

Purpose of the Study:

  • To investigate the conservation of the TH-binding motif in human and animal selenodeiodinases.
  • To analyze the shared TH-binding domain across THPC, CSTT, TR, and deiodinases.
  • To understand the evolutionary basis for diverse protein interactions with TH.

Main Methods:

  • Comparative sequence analysis of 10,229 protein sequences including THPC, CSTT, TR, and deiodinases.
  • Identification and characterization of conserved residues within the 49-position TH-binding motif.
  • Alignment of conserved residues in deiodinase active centers with the TH-binding motif.

Main Results:

  • 15 out of 49 positions in the TH-binding motif are very highly conserved, and 18 are highly conserved across all analyzed proteins.
  • A highly conserved 5-residue core motif (W/F/Y, L/I/V/M, I/V/M/L, P, L/V/I/M) was identified.
  • Multiple conserved residues in deiodinases, including those in active centers, align with the shared TH-binding motif and THPC consensus sequences.

Conclusions:

  • A common, evolutionarily conserved TH-binding domain exists in THPC, CSTT, TR, and deiodinases.
  • This shared domain, likely originating from an ancestral gene, underlies the interaction of diverse proteins with thyroid hormone.
  • The findings provide insights into the molecular mechanisms of TH transport, signaling, and metabolism.