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Primary structure of bovine thyroglobulin deduced from the sequence of its 8,431-base complementary DNA

Nature volume 316, pages 647–651 (1985)Cite this article

Abstract

In mammals, an adequate supply of thyroid hormones is essential for normalgrowth and neurological development. The biosynthesis of thyroid hormones involves an iodinated precursor protein, thyroglobulin, which may be considered an extreme example of a pro-hormone1. Thyroglobulin is a dimeric glycoprotein of relative molecular mass (Mr) 660,000 (660K), which is secreted by the thyrocyte and stored in the lumen of the thyroid follicle. The hormonogenic reaction is extracellular, and involves iodination of tyrosyl residues of thyroglobulin and the intramolecular coupling of a subset of these into thyroxine (T4) and triiodothyronine (T3), which remain part of the polypeptide chain. Secretion of hormones results from the endocytosis of thyroglobulin followed by its complete hydrolysis in lysosomes. Considering that the maximum yield of hormones is ∼6–8 per 660K protein2, the whole process is apparently wasteful. However, the efficiency of thyroglobulin as a thyroid hormone precursor is extremely high when the supply of iodine is short; in such conditions, almost all the iodine incorporated is found in iodothyronines3. Hence it is suggested that the thyroglobulin structure has evolved to allow for the preferential and efficient iodination and coupling of the hormonogenic tyrosines. Here we report the complete primary structure of bovine thyroglobulin, derived from the sequence of its 8,431-base-pair complementary DNA. The 2,769-amino-acid sequence is characterized by a pattern of imperfect repeats derived from three cysteine-rich motifs. Four hormonogenic tyrosines have been precisely localized near the amino and carboxyl ends of the protein.

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Authors and Affiliations

  1. Institut de Recherche Interdisciplinaire et Service de Chimie Clinique, Faculté de Médecine, Université Libre de Bruxelles, Campus Erasme, 808 route de Lennik, 1070, Bruxelles, Belgium

    Luc Mercken, Marie-Jeanne Simons, Stéphane Swillens, Marc Massaer & Gilbert Vassart

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Mercken, L., Simons, MJ., Swillens, S. et al. Primary structure of bovine thyroglobulin deduced from the sequence of its 8,431-base complementary DNA. Nature 316, 647–651 (1985). https://doi.org/10.1038/316647a0

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