A thyroid hormone binding motif is evolutionarily conserved in apolipoproteins

Area of Science:

• Biochemistry
• Molecular Biology
• Evolutionary Biology

Background:

• High-density lipoproteins (HDL) are primary carriers of thyroid hormones in plasma.
• Thyroid hormone binding to HDL is mediated by apolipoproteins, sharing sequence homology with known transport proteins.
• A conserved 5-residue hydrophobic motif within apolipoproteins is identified as a potential thyroid hormone binding site.

Purpose of the Study:

• To investigate the evolutionary conservation of thyroid hormone binding to HDL apolipoproteins.
• To identify the specific structural features responsible for thyroid hormone interaction with HDL.
• To determine if HDL-mediated thyroid hormone transport is an ancient mechanism.

Main Methods:

• Analysis of apolipoprotein sequences for conservation of a 5-residue hydrophobic motif.
• Testing the thyroid hormone binding properties of bovine apo A-I and rabbit apo E.
• Comparative analysis of motif conservation across species and in relation to mutations.

Main Results:

• A highly conserved 5-residue hydrophobic motif "Y, L/I/M, X, X, V/L/I" was identified in HDL apolipoproteins.
• Animal apolipoproteins (bovine apo A-I, rabbit apo E) exhibit thyroid hormone binding properties similar to human counterparts.
• The conserved motif is protected from naturally occurring mutations, suggesting functional importance.

Conclusions:

• Thyroid hormone binding to HDL apolipoproteins is conserved throughout the animal phylum.
• This interaction represents the earliest form of plasma transport for thyroid hormones.
• The structural integrity of the identified hormone-binding domain is critical for apolipoprotein function.