7n4y

Publication Abstract from PubMed

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 A resolution in the core region and 2.6 A 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.

The structure of natively iodinated bovine thyroglobulin.,Kim K, Kopylov M, Bobe D, Kelley K, Eng ET, Arvan P, Clarke OB Acta Crystallogr D Struct Biol. 2021 Nov 1;77(Pt 11):1451-1459. doi:, 10.1107/S2059798321010056. Epub 2021 Oct 29. PMID:34726172^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.