The sites of thyroid hormone formation in rabbit thyroglobulin.

Dunn, John T.; Anderson, Peggy; Fox, Jay W.; Fassler, C.; Dunn, Ann D.; Hite, L A; Moore, Raymond C.

doi:10.1016/s0021-9258(18)45475-0

Cited by 57 publications

(2 citation statements)

References 13 publications

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“…This has been an extremely successful approach to the identification of DIT acceptors, which represent the sites of hormone formation. However, biochemical approaches have been less definitive in identifying the specific donor partner(s) that yield their iodophenolic side chain to be converted to dehydroalanine in the process of forming thyroid hormone at Tg acceptor sites (Marriq et al, 1991;Dedieu et al, 2011;Dunn et al, 1987;Palumbo, 1987;Ohmiya et al, 1990;Palumbo et al, 1990;Xiao et al, 1996;Gentile et al, 1997). In the present study, we examined the structure of iodinated bovine Tg.…”

Section: Discussionmentioning

confidence: 99%

The structure of natively iodinated bovine thyroglobulin

Kim¹,

Kopylov²,

Bobe³

et al. 2021

Acta Cryst Sect D Struct Biol

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Thyroglobulin is a homodimeric glycoprotein that is essential for the generation of thyroid hormones in vertebrates. Upon secretion into the lumen of follicles in the thyroid gland, tyrosine residues within the protein become iodinated to produce monoiodotyrosine (MIT) and diiodotyrosine (DIT). A subset of evolutionarily conserved pairs of DIT (and MIT) residues can then engage in oxidative coupling reactions that yield either thyroxine (T4; produced from coupling of a DIT `acceptor' with a DIT `donor') or triiodothyronine (T3; produced from coupling of a DIT acceptor with an MIT donor). Although multiple iodotyrosine residues have been identified as potential donors and acceptors, the specificity and structural context of the pairings (i.e. which donor is paired with which acceptor) have remained unclear. Here, single-particle cryogenic electron microscopy (cryoEM) was used to generate a high-resolution reconstruction of bovine thyroglobulin (2.3 Å resolution in the core region and 2.6 Å overall), allowing the structural characterization of two post-reaction acceptor–donor pairs as well as tyrosine residues modified as MIT and DIT. A substantial spatial separation between donor Tyr149 and acceptor Tyr24 was observed, suggesting that for thyroxine synthesis significant peptide motion is required for coupling at the evolutionarily conserved thyroglobulin amino-terminus.

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Section: Discussionmentioning

confidence: 99%

The structure of natively iodinated bovine thyroglobulin

Kim¹,

Kopylov²,

Bobe³

et al. 2021

Acta Cryst Sect D Struct Biol

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“…Based on the knowledge that the extreme NH2 terminus of mature Tg is well conserved between different species (Rawitch et al, 1984;Dunn et al, 1987), a peptide was synthesized representing the first 15 amino acids of rat Tg, and this peptide was coupled to the activated carrier protein acceptor, KLH (Pierce, Rockford, IL). A polyclonal antibody directed against this peptide was raised in chicken, and IgY purified from eggs was generated for use in subsequent studies.…”

Section: Antibodiesmentioning

confidence: 99%

An endoplasmic reticulum storage disease causing congenital goiter with hypothyroidism.

Kim

Kwon

Arvan

1996

The Journal of Cell Biology

108

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Abstract. In humans, deficient thyroglobulin (Tg, the thyroid prohormone) is an important cause of congenital hypothyroid goiter; further, homozygous mice expressing two cog~cog alleles (linked to the Tg locus) exhibit the same phenotype. Tg mutations might affect multiple different steps in thyroid hormone synthesis; however, the microscopic and biochemical phenotype tends to involve enlargement of the thyroid ER and accumulation of protein bands of Mr < 100. To explore further the cell biology of this autosomal recessive illness, we have examined the folding and intracellular

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Chemie und Biologie der Schilddrüsenhormon‐Biosynthese und ‐Wirkung

Mondal¹,

Raja²,

Schweizer

et al. 2016

Angewandte Chemie

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Schilddrüsenhormone (THs) werden von der Schilddrüse abgegeben. Sie kontrollieren Fett‐, Kohlenhydrat‐ und Proteinmetabolismus, Herzfrequenz, neuronale Entwicklung sowie kardiovaskuläre, renale und neuronale Funktionen. Die Schilddrüse produziert überwiegend l‐Thyroxin (T4), das als Prohormon fungiert. Durch 5′‐Deiodierung, katalysiert von Iodthyronin‐Deiodasen, wird aktives T3 gebildet, das an den nukleären Schilddrüsenhormon‐Rezeptor bindet. In diesem Aufsatz fassen wir sowohl die grundlegende Chemie und Biologie als auch die neuesten Erkenntnisse zur TH‐Biosynthese, zum Plasmatransport und zur Internalisierung der THs in die Zielorgane, zur Deiodierung und zu einer Vielzahl anderer Enzym‐vermittelter Stoffwechselwege zusammen. Zudem erörtern wir Schilddrüsenhormon‐Rezeptoren, verschiedene Schilddrüsen‐bedingte Krankheiten und deren Therapien.

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The sites of thyroid hormone formation in rabbit thyroglobulin.

Cited by 57 publications

References 13 publications

The structure of natively iodinated bovine thyroglobulin

The structure of natively iodinated bovine thyroglobulin

An endoplasmic reticulum storage disease causing congenital goiter with hypothyroidism.

Chemie und Biologie der Schilddrüsenhormon‐Biosynthese und ‐Wirkung

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