Cryo-EM structure of native human thyroglobulin
Adaixo, Ricardo ; Steiner, Eva M. LU
; Righetto, Ricardo R.
; Schmidt, Alexander
; Stahlberg, Henning
and Taylor, M.I
(2022)
In Nature Communications
- 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 Å resolution. The... (More)
- 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. (Less)
- Abstract (Swedish)
- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/32aa1633-6f6a-4496-aaaa-300cfae71492
- author
- Adaixo, Ricardo
; Steiner, Eva M.
LU
; Righetto, Ricardo R.
; Schmidt, Alexander
; Stahlberg, Henning
and Taylor, M.I
- publishing date
- 2022
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Nature Communications
- article number
- 61
- publisher
- Nature Publishing Group
- external identifiers
-
- scopus:85122853998
- ISSN
- 2041-1723
- DOI
- 10.1038/s41467-021-27693-8
- language
- English
- LU publication?
- no
- id
- 32aa1633-6f6a-4496-aaaa-300cfae71492
- date added to LUP
- 2024-06-19 13:21:48
- date last changed
- 2024-06-20 08:38:14
@article{32aa1633-6f6a-4496-aaaa-300cfae71492,
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 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.}},
author = {{Adaixo, Ricardo and Steiner, Eva M. and Righetto, Ricardo R. and Schmidt, Alexander and Stahlberg, Henning and Taylor, M.I}},
issn = {{2041-1723}},
language = {{eng}},
publisher = {{Nature Publishing Group}},
series = {{Nature Communications}},
title = {{Cryo-EM structure of native human thyroglobulin}},
url = {{http://dx.doi.org/10.1038/s41467-021-27693-8}},
doi = {{10.1038/s41467-021-27693-8}},
year = {{2022}},
}