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TitleThe structure of natively iodinated bovine thyroglobulin.
Journal, issue, pagesActa Crystallogr D Struct Biol, Vol. 77, Issue Pt 11, Page 1451-1459, Year 2021
Publish dateNov 1, 2021
AuthorsKookjoo Kim / Mykhailo Kopylov / Daija Bobe / Kotaro Kelley / Edward T Eng / Peter Arvan / Oliver B Clarke /
PubMed AbstractThyroglobulin 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 ...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 (T; produced from coupling of a DIT `acceptor' with a DIT `donor') or triiodothyronine (T; 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.
External linksActa Crystallogr D Struct Biol / PubMed:34726172 / PubMed Central
MethodsEM (single particle)
Resolution2.61 Å
Structure data

24181

7n4y

EMDB-24181, PDB-7n4y:
The structure of bovine thyroglobulin with iodinated tyrosines
Method: EM (single particle) / Resolution: 2.61 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

ChemComp-HOH:
WATER / Water

Source
  • bos indicus x bos taurus (hybrid cattle)
KeywordsHORMONE / thyroid hormone synthesis

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