Cryo-EM structure of native human thyroglobulin

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Cryo-EM structure of native human thyroglobulin. / Adaixo, Ricardo; Steiner, Eva M.; Righetto, Ricardo D.; Schmidt, Alexander; Stahlberg, Henning; Taylor, Nicholas M. I.

In: Nature Communications, Vol. 13, No. 1, 61, 2022.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Adaixo, R, Steiner, EM, Righetto, RD, Schmidt, A, Stahlberg, H & Taylor, NMI 2022, 'Cryo-EM structure of native human thyroglobulin', Nature Communications, vol. 13, no. 1, 61. https://doi.org/10.1038/s41467-021-27693-8

APA

Adaixo, R., Steiner, E. M., Righetto, R. D., Schmidt, A., Stahlberg, H., & Taylor, N. M. I. (2022). Cryo-EM structure of native human thyroglobulin. Nature Communications, 13(1), [61]. https://doi.org/10.1038/s41467-021-27693-8

Vancouver

Adaixo R, Steiner EM, Righetto RD, Schmidt A, Stahlberg H, Taylor NMI. Cryo-EM structure of native human thyroglobulin. Nature Communications. 2022;13(1). 61. https://doi.org/10.1038/s41467-021-27693-8

Author

Adaixo, Ricardo ; Steiner, Eva M. ; Righetto, Ricardo D. ; Schmidt, Alexander ; Stahlberg, Henning ; Taylor, Nicholas M. I. / Cryo-EM structure of native human thyroglobulin. In: Nature Communications. 2022 ; Vol. 13, No. 1.

Bibtex

@article{fe906385af0c435291b3ef7707e77fd7,
title = "Cryo-EM structure of native human thyroglobulin",
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 (T3) and thyroxine (T4) 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 {\AA} 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.",
author = "Ricardo Adaixo and Steiner, {Eva M.} and Righetto, {Ricardo D.} and Alexander Schmidt and Henning Stahlberg and Taylor, {Nicholas M. I.}",
note = "Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
doi = "10.1038/s41467-021-27693-8",
language = "English",
volume = "13",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",
number = "1",

}

RIS

TY - JOUR

T1 - Cryo-EM structure of native human thyroglobulin

AU - Adaixo, Ricardo

AU - Steiner, Eva M.

AU - Righetto, Ricardo D.

AU - Schmidt, Alexander

AU - Stahlberg, Henning

AU - Taylor, Nicholas M. I.

N1 - Publisher Copyright: © 2022, The Author(s).

PY - 2022

Y1 - 2022

N2 - 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 (T3) and thyroxine (T4) 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.

AB - 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 (T3) and thyroxine (T4) 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.

U2 - 10.1038/s41467-021-27693-8

DO - 10.1038/s41467-021-27693-8

M3 - Journal article

C2 - 35013249

AN - SCOPUS:85122853998

VL - 13

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 61

ER -

ID: 290667951