Structure Report for: 7B75

Ricardo Adaixo, Eva M. Steiner, Ricardo D. Righetto, Alexander Schmidt, Henning Stahlberg and Nicholas M. I. Taylor

Title: Cryo-EM structure of native human thyroglobulin
Adaixo R, Steiner EM, Righetto RD, Schmidt A, Stahlberg H, Taylor NMI
Ref: Nat Commun, 13:61, 2022 : PubMed
Abstract


ESTHER: Adaixo_2022_Nat.Commun_13_61
PubMedSearch: Adaixo 2022 Nat.Commun 13 61
PubMedID: 35013249
Gene_locus related to this paper: human-TG

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(3)) and thyroxine (T(4)) 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 A 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.



        

Title: Cryo-EM structure of native human thyroglobulin
Adaixo R, Steiner EM, Righetto RD, Schmidt A, Stahlberg H, Taylor NMI
Ref: Biorxiv, :, 2021 : PubMed
Abstract


ESTHER: Adaixo_2021_Biorxiv__
PubMedSearch: Adaixo 2021 Biorxiv
Gene_locus related to this paper: human-TG

Abstract

The thyroglobulin (Tg) protein is essential to thyroid hormone synthesis, playing a vital role in the regulation of metabolism, development and growth. Its structure is conserved among vertebrates. Tg is delivered through the secretory pathway of the thyroid follicular unit to the central colloid depository, where it is iodinated at specific tyrosine sites to form mono- or diiodotyrosine, which combine to produce triiodothyronine (T3) and thyroxine (T4), respectively. Synthesis of these hormones depends on the precise 3D structure of Tg, which has remained unknown despite decades of research. Here, we present the cryo-electron microscopy structure of human thyroglobulin (hTg) to a global resolution of 3.2 A. The structure provides detailed information on the location of the hTg hormonogenic sites and reveals the position as well as the role of many of its glycosylation sites. Our results offer structural insight into thyroid hormonogenesis and provide a fundamental understanding of clinically relevant hTg mutations, which can improve treatment of thyroid diseases.