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Vol 70, No 1 (2019)
Review paper
Submitted: 2018-08-04
Accepted: 2018-09-16
Published online: 2019-02-22
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Glycosylation of thyroid-stimulating hormone receptor [Glikozylacja receptora hormonu tyreotropowego]

Paulina Korta1, Ewa Pocheć1
DOI: 10.5603/EP.a2018.0077
·
Pubmed: 30843179
·
Endokrynol Pol 2019;70(1):86-100.
Affiliations
  1. Deptartment of Glycoconjugate Biochemistry, Institute of Zoology and Biomedical Research, Jagiellonian University, Krakow, Poland

open access

Vol 70, No 1 (2019)
Review Article
Submitted: 2018-08-04
Accepted: 2018-09-16
Published online: 2019-02-22

Abstract

Thyroid-stimulating hormone receptor (TSHR) is a typical membrane receptor with 7-transmembrane helix domain (7TMR), coupled to the G protein. The mature receptor, present in the cell membrane, is composed of the A subunit comprising a large extracellular domain, and the B subunit, which consists of a short extracellular fragment anchored in the cell membrane and an intracellular part. The TSH receptor is subject to numerous post-translational modifications that determine its final structure and significantly affect its activity. One of them is glycosylation. TSHR is abundantly N-glycosylated, due to the presence of six N-glycosylation sites in the extracellular domain (Asn77, Asn99, Asn113, Asn177, Asn198, Asn302), mostly evolutionarily conserved. N-glycans constitute 30–40% of the receptor molecular weight. The glycans are necessary for the receptor trafficking to the plasma membrane and binding of TSH to the receptor. Fucosylated and sialylated N-oligosaccharides were found on TSHR molecules. The increased sialylation of TSHR glycans correlates positively with the receptor binding ability and prolongs the time of receptor incorporation into the cell membrane. TSHR is the main autoantigen in Graves’ disease (GD), one of the thyroid autoimmune diseases. One hypothesis assumes that the higher N-glycosylation of THSR in human compared to animals influences the breaking of autotolerance and GD development. N-oligosaccharides are the important part of THSR molecule, necessary for the proper functioning of receptors and probably involved in thyroid autoimmunity in GD.

Abstract

Thyroid-stimulating hormone receptor (TSHR) is a typical membrane receptor with 7-transmembrane helix domain (7TMR), coupled to the G protein. The mature receptor, present in the cell membrane, is composed of the A subunit comprising a large extracellular domain, and the B subunit, which consists of a short extracellular fragment anchored in the cell membrane and an intracellular part. The TSH receptor is subject to numerous post-translational modifications that determine its final structure and significantly affect its activity. One of them is glycosylation. TSHR is abundantly N-glycosylated, due to the presence of six N-glycosylation sites in the extracellular domain (Asn77, Asn99, Asn113, Asn177, Asn198, Asn302), mostly evolutionarily conserved. N-glycans constitute 30–40% of the receptor molecular weight. The glycans are necessary for the receptor trafficking to the plasma membrane and binding of TSH to the receptor. Fucosylated and sialylated N-oligosaccharides were found on TSHR molecules. The increased sialylation of TSHR glycans correlates positively with the receptor binding ability and prolongs the time of receptor incorporation into the cell membrane. TSHR is the main autoantigen in Graves’ disease (GD), one of the thyroid autoimmune diseases. One hypothesis assumes that the higher N-glycosylation of THSR in human compared to animals influences the breaking of autotolerance and GD development. N-oligosaccharides are the important part of THSR molecule, necessary for the proper functioning of receptors and probably involved in thyroid autoimmunity in GD.

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Keywords

TSHR; N-glycosylation; sialylation; thyroid; Graves’ disease

About this article
Title

Glycosylation of thyroid-stimulating hormone receptor [Glikozylacja receptora hormonu tyreotropowego]

Journal

Endokrynologia Polska

Issue

Vol 70, No 1 (2019)

Article type

Review paper

Pages

86-100

Published online

2019-02-22

Page views

3571

Article views/downloads

1830

DOI

10.5603/EP.a2018.0077

Pubmed

30843179

Bibliographic record

Endokrynol Pol 2019;70(1):86-100.

Keywords

TSHR
N-glycosylation
sialylation
thyroid
Graves’ disease

Authors

Paulina Korta
Ewa Pocheć

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