7N4Y

The structure of bovine thyroglobulin with iodinated tyrosines

7N4Y の概要

• エントリーDOI: 10.2210/pdb7n4y/pdb
• EMDBエントリー: 24181
• 分子名称: Thyroglobulin, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• 機能のキーワード: thyroid hormone synthesis, hormone
• 由来する生物種: Bos indicus x Bos taurus (Hybrid cattle)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 612399.54

構造登録者

Kim, K.,Clarke, O.B. (登録日: 2021-06-04, 公開日: 2021-11-10, 最終更新日: 2025-06-04)

主引用文献

Kim, K.,Kopylov, M.,Bobe, D.,Kelley, K.,Eng, E.T.,Arvan, P.,Clarke, O.B.
The structure of natively iodinated bovine thyroglobulin.
Acta Crystallogr D Struct Biol, 77:1451-1459, 2021

PubMed Abstract: 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.

PubMed: 34726172
DOI: 10.1107/S2059798321010056

実験手法

ELECTRON MICROSCOPY (2.61 Å)