7B75

Cryo-EM Structure of Human Thyroglobulin

7B75 の概要

• エントリーDOI: 10.2210/pdb7b75/pdb
• EMDBエントリー: 12073
• 分子名称: Thyroglobulin, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, beta-D-mannopyranose-(1-4)-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: thyroglobulin, t3 and t4 hormonogenesis, cryo-em, hormone
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 621041.80

構造登録者

Adaixo, R.,Righetto, R.,Steiner, E.M.,Taylor, N.M.I.,Stahlberg, H. (登録日: 2020-12-09, 公開日: 2021-12-29, 最終更新日: 2024-10-16)

主引用文献

Adaixo, R.,Steiner, E.M.,Righetto, R.D.,Schmidt, A.,Stahlberg, H.,Taylor, N.M.I.
Cryo-EM structure of native human thyroglobulin.
Nat Commun, 13:61-61, 2022

PubMed Abstract: The thyroglobulin (TG) protein is essential to thyroid hormone synthesis, plays a vital role in the regulation of metabolism, development and growth and serves as intraglandular iodine storage. Its architecture is conserved among vertebrates. Synthesis of triiodothyronine (T) and thyroxine (T) hormones depends on the conformation, iodination and post-translational modification of TG. Although structural information is available on recombinant and deglycosylated endogenous human thyroglobulin (hTG) from patients with goiters, the structure of native, fully glycosylated hTG remained unknown. Here, we present the cryo-electron microscopy structure of native and fully glycosylated hTG from healthy thyroid glands to 3.2 Å resolution. The structure provides detailed information on hormonogenic and glycosylation sites. We employ liquid chromatography-mass spectrometry (LC-MS) to validate these findings as well as other post-translational modifications and proteolytic cleavage sites. Our results offer insights into thyroid hormonogenesis of native hTG and provide a fundamental understanding of clinically relevant mutations.

PubMed: 35013249
DOI: 10.1038/s41467-021-27693-8

実験手法

ELECTRON MICROSCOPY (3.2 Å)