Distinctive binding and structural properties of piscine transthyretin.
The thyroid hormone binding protein transthyretin (TTR) forms a macromolecular complex with the retinol-specific carrier retinol binding protein (RBP) in the blood of higher vertebrates. Piscine TTR is shown here to exhibit high binding affinity for L-thyroxine and negligible affinity for RBP. The 1.56 A resolution X-ray structure of sea bream TTR, compared with that of human TTR, reveals a high degree of conservation of the thyroid hormone binding sites. In contrast, some amino acid differences in discrete regions of sea bream TTR appear to be responsible for the lack of protein-protein recognition, providing evidence for the crucial role played by a limited number of residues in the interaction between RBP and TTR. Overall, this study makes it possible to draw conclusions on evolutionary relationships for RBPs and TTRs of phylogenetically distant vertebrates.
Folli
Claudia
C
Department of Biochemistry and Molecular Biology, University of Parma, Parco Area delle Scienze 23/A, 43100 Parma, Italy.
Pasquato
Nicola
N
Ramazzina
Ileana
I
Battistutta
Roberto
R
Zanotti
Giuseppe
G
Berni
Rodolfo
R
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002347:Carps; D002645:Chickens; D018360:Crystallography, X-Ray; D005453:Fluorescence; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011228:Prealbumin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012177:Retinol-Binding Proteins / Q000378:metabolism; D021541:Sea Bream; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013974:Thyroxine / Q000378:metabolism
D011228:Prealbumin; D011994:Recombinant Proteins; D012177:Retinol-Binding Proteins; D013974:Thyroxine