7B75

Cryo-EM Structure of Human Thyroglobulin

Summary for 7B75

• Entry DOI: 10.2210/pdb7b75/pdb
• EMDB information: 12073
• Descriptor: 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)
• Functional Keywords: thyroglobulin, t3 and t4 hormonogenesis, cryo-em, hormone
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 621041.80

Authors

Adaixo, R.,Righetto, R.,Steiner, E.M.,Taylor, N.M.I.,Stahlberg, H. (deposition date: 2020-12-09, release date: 2021-12-29, Last modification date: 2024-10-16)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (3.2 Å)