Glycosylation of thyroid-stimulating hormone receptor

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.

Irisin as a Multifunctional Protein: Implications for Health and Certain Diseases

“…The attachment of carbohydrates, which is a multi-stage process regulated by hundreds of enzymes, leads to a great heterogeneity in the glycan structures. Oligosaccharides affect the physicochemical properties of proteins, are necessary to obtain the accurate conformation of proteins, provide protection against proteolysis, and are important for their biological functions in different metabolic processes [10]. FNDC5 is an N -glycosylated protein and contains oligosaccharides attached to the asparagine residue in the Asn–X–Ser/Thr sequence (where X is any amino acid except proline), via a N -acetylglucosamine residue (GlcNAc) [11].…”

Receptor autoimmunity: diagnostic and therapeutic implications

“…The full-length TSHR undergoes other complex post-translational processing, including glycosylation, phosphorylation, and multimerization [12,18]: the multiplicity of TSHR forms probably explains the different phenotypes of GD (thyroid disease only, eye disease only, or 'complete' GD) [12].…”

Superiority of the Non-Glycosylated Form over the Glycosylated Form of Irisin in the Attenuation of Adipocytic Meta-Inflammation: A Potential Factor in the Fight against Insulin Resistance

“…Irisin is a small protein with a length of only 112 amino acids and results from the proteolytic cleavage of the fibronectin type III domain containing five proteins (FNDC5) [10], which has two N -glycosylation sites [25]. Glycosylation affects the properties of numerous proteins and can affect the modulation of many biological processes [26]. For example, irisin glycosylation affects its half-life by stabilizing its structure [27,28].…”