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Thyroglobulin structure-function. The amino acid sequence surrounding thyroxine.

A B Rawitch, S B Chernoff, M R Litwer

    The Journal of Biological Chemistry
    |February 25, 1983
    PubMed
    Summary
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    Researchers isolated a thyroxine (T4)-containing peptide, Tryp-T4, revealing a key site for T4 biosynthesis within bovine thyroglobulin. This peptide is crucial for understanding thyroid hormone production.

    Area of Science:

    • Biochemistry
    • Endocrinology
    • Molecular Biology

    Background:

    • Thyroglobulin is a large glycoprotein essential for thyroid hormone synthesis.
    • Iodination of thyroglobulin is a critical step in producing thyroxine (T4) and triiodothyronine (T3).
    • Identifying specific hormonogenic sites within thyroglobulin is key to understanding thyroid hormone regulation.

    Purpose of the Study:

    • To isolate and characterize the specific peptide sequence within bovine thyroglobulin responsible for thyroxine (T4) incorporation.
    • To determine the amino acid sequence of the T4-containing peptide and its location within the parent protein fragment.
    • To establish the role of this unique sequence in thyroxine biosynthesis and thyroid hormone production.

    Main Methods:

    • Isolation of a 19-residue peptide (Tryp-T4) from a tryptic digest of an iodine-enriched fragment of 19S bovine thyroglobulin.

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  • Amino acid sequencing of the isolated Tryp-T4 peptide to determine its primary structure.
  • Analysis of the peptide's carboxyl-terminal sequence for structural motifs, such as beta-turns.

    • Main Results:

    • A single 19-residue peptide, Tryp-T4, containing thyroxine (T4) was isolated and identified.
    • The amino acid sequence NH2-Asn-Ile-Phe-Glu-T4-Gln-Val-Asp-Ala-Gln-Pro-Leu-Arg-Pro-Cys-Glu-Leu-Gln-Arg-COOH was determined for Tryp-T4.
    • This peptide represents the primary site of iodination and contains at least 30% of the T4 in 19S bovine thyroglobulin.
    • The carboxyl-terminal region exhibited a high probability of a beta-turn structure.

    Conclusions:

    • A specific, unique amino acid sequence within thyroglobulin is directly involved in thyroxine biosynthesis.
    • The identified Tryp-T4 peptide represents a major hormonogenic site within the thyroglobulin protein.
    • These findings advance the understanding of the molecular mechanisms underlying thyroid hormone production.