Thyroid hormone-interacting cell and plasma proteins share a common motif

Area of Science:

• Biochemistry
• Molecular Biology
• Endocrinology

Background:

• Thyroid hormone (TH) binding proteins, including plasma carriers (THPC), cell surface transporters (CMTTH), and nuclear receptors (THR), play crucial roles in TH regulation.
• A conserved TH-binding consensus sequence was previously identified in THPCs.
• The presence of such a shared sequence in CMTTH and THR was hypothesized but not fully investigated.

Purpose of the Study:

• To investigate the hypothesis that a conserved thyroid hormone (TH)-binding consensus sequence is shared among TH plasma carriers (THPC), cell surface TH transporters (CMTTH), and TH nuclear receptors (THR).
• To identify and compare conserved residues and motifs across these diverse TH-binding proteins.
• To elucidate the evolutionary basis of TH binding in different protein families.

Main Methods:

• Generated consensus sequences for CMTTH (8,691 sequences) and THR (624 sequences).
• Analyzed and compared the conservation of residues within the consensus sequences of THPC, CMTTH, and THR.
• Identified and confirmed the presence of a specific 5-residue TH-binding motif across a large dataset of 9,741 sequences.

Main Results:

• Identified significant matches in highly conserved residues between CMTTH and THPC, and between THR and THPC.
• Found a conserved 5-residue TH-binding motif (Trp/Phe/Tyr, Leu/Ile/Val/Met, Ile/Val/Met/Leu, Pro, Leu/Val/Ile/Met) present in THPCs, CMTTH, and THR.
• Demonstrated phylogenetic conservation of this homologous region across genetically and functionally diverse proteins.

Conclusions:

• Proteins involved in thyroid hormone transport and reception share a common homologous region responsible for TH binding.
• This shared conserved sequence suggests a common evolutionary origin for these diverse TH-binding proteins.
• The findings provide insights into the molecular mechanisms underlying thyroid hormone regulation and its evolutionary history.