Chapter 11 The Glycoprotein Hormone Family: Structure and Function of the Carbohydrate Chains

Bielińska, Małgorzata; Boime, Irving

doi:10.1016/s0167-7306(08)60605-5

Cited by 8 publications

(14 citation statements)

References 199 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The majority of the Nglycans contained 9 to 10 Man residues, independent on the chosen culturing process, whereby Man 9 GlcNAc 2 nearly only represents the typical yeast isomer. However, culturing conditions did influence the molar ratio within Man [8][9][10][11][12] GlcNAc 2 . It should be noted that previous NMR structural studies of yeast glycoprotein N-glycans were always carried out on Man x (P y )GlcNAc 1 compounds; in the present investigation NMR data of Man x (P y )GlcNAc 2 compounds are presented.…”

Section: Discussionmentioning

confidence: 96%

“…A random distribution of these O-glycans among the attachment sites has been suggested [9]. Over the years many studies have appeared demonstrating the crucial importance of the glycosylation of hCG for its biological functioning (for a review, see e.g., [10]). In reaching conclusions, site-directed mutagenesis of specific (glycosylation) sites in urinary hCG applying different host cell systems played a major role.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Characterization of the N-linked oligosaccharides from human chorionic gonadotropin expressed in the methylotrophic yeast Pichia pastoris

et al. 2006

View full text Add to dashboard Cite

Human chorionic gonadotropin (hCG) is a heterodimeric, placental glycoprotein hormone involved in the maintenance of the corpus luteum during the first trimester of pregnancy. Biologically active hCG has been successfully expressed in the yeast Pichia pastoris (phCG). In the context of structural studies and therapeutic applications of phCG, detailed information about its glycosylation pattern is a prerequisite. To this end N-glycans were released with peptide-N 4 -(N-acetyl-β-glucosaminyl)asparagine amidase F and fractionated via anion-exchange chromatography (Resource Q) yielding both neutral (80%) and charged, phosphate-containing (20%) high-mannosetype structures. Subfractionations were carried out via normal phase (Lichrosorb-NH 2 ) and high-pH anion-exchange (CarboPac PA-1) chromatography. Structural analyses of the released N-glycans were carried out by using HPLC profiling of fluorescent 2-aminobenzamide derivatives, MALDI-TOF mass spectrometry, and 500-MHz 1 H-NMR spectroscopy. Detailed neutral oligosaccharide structures, in the range of Man 8 GlcNAc 2 to Man 11 GlcNAc 2 including molecular isomers, could be established, and structures up to Man 15 GlcNAc 2 were indicated. Phosphatecontaining oligosaccharides ranged from Man 9 PGlcNAc 2 to Man 13 PGlcNAc 2 . Mannosyl O-glycans were not detected. Profiling studies carried out on different production batches showed that the oligosaccharide structures are similar, but their relative amounts varied with the culturing media.

show abstract

Section: Discussionmentioning

confidence: 96%

mentioning

confidence: 99%

Characterization of the N-linked oligosaccharides from human chorionic gonadotropin expressed in the methylotrophic yeast Pichia pastoris

et al. 2006

View full text Add to dashboard Cite

show abstract

“…Initially, physicochemical and enzymatic studies have identified amino acids as well as carbohydrate portions on both subunits which contribute to dimerization of two subunits, receptor binding, and signal transduction. These approaches, which are summarized in excellent reviews (5,14,39,140,171,187), have been instrumental in gaining an initial understanding of glycoprotein hormone structure-function relationships and continue to provide valuable information to the present time. Other valuable strategies rely primarily on epitope mapping or the use of synthetic peptides (39,88,94,129).…”

Section: A Methodologymentioning

confidence: 99%

“…Deglycosylation of hCG and bovine TSH has long been known to result in increased receptor binding but loss in efficient signal transduction. Many reviews have covered the role of carbohydrate chains in glycoprotein hormone assembly, secretion, and bioactivity, and the reader is invited to refer to them for more detailed information (4,14,146,188,222). It appears that glycosylation can play a role in the life span of the hormone through different glycan structure.…”

Section: Function Of Carbohydrate Chainsmentioning

confidence: 99%

Thyroid-Stimulating Hormone and Thyroid-Stimulating Hormone Receptor Structure-Function Relationships

Szkudlinski

Frémont²,

Ronin³

et al. 2002

Physiological Reviews

401

256

View full text Add to dashboard Cite

This review focuses on recent advances in the structure-function relationships of thyroid-stimulating hormone (TSH) and its receptor. TSH is a member of the glycoprotein hormone family constituting a subset of the cystine-knot growth factor superfamily. TSH is produced by the pituitary thyrotrophs and released to the circulation in a pulsatile manner. It stimulates thyroid functions using specific membrane TSH receptor (TSHR) that belongs to the superfamily of G protein-coupled receptors (GPCRs). New insights into the structure-function relationships of TSH permitted better understanding of the role of specific protein and carbohydrate domains in the synthesis, bioactivity, and clearance of this hormone. Recent progress in studies on TSHR as well as studies on the other GPCRs provided new clues regarding the molecular mechanisms of receptor activation. Such advances are a result of extensive site-directed mutagenesis, peptide and antibody approaches, detailed sequence analyses, and molecular modeling as well as studies on naturally occurring gain- and loss-of-function mutations. This review integrates expanding information on TSH and TSHR structure-function relationships and summarizes current concepts on ligand-dependent and -independent TSHR activation. Special emphasis has been placed on TSH domains involved in receptor recognition, constitutive activity of TSHR, new insights into the evolution of TSH bioactivity, and the development of high-affinity TSH analogs. Such structural, physiological, pathophysiological, evolutionary, and therapeutic implications of TSH-TSHR structure-function studies are frequently discussed in relation to concomitant progress made in studies on gonadotropins and their receptors.

show abstract

“…The presence of the terminal GalNAc with/without sulfate is important for serum clearance of the hormones by the Kupffer cells of the liver and acts as an important feedback signal to ensure that more LH is produced by the pituitary gland and subsequent induction of ovulation via the LH/CG receptor in the ovary. Notably, the enzymes involved in the attachment of GalNAc and sulfate to the LH fluctuate according to the levels of estrogen in the circulation (Bielinska and Boime, 1995).…”

Section: Hormone Functionmentioning

confidence: 99%

Structure/function of N ‐glycans

Brooks

Dwek

2005

Encyclopedia of Genetics, Genomics, Proteomics and Bioinformatics

View full text Add to dashboard Cite

show abstract

Chapter 11 The Glycoprotein Hormone Family: Structure and Function of the Carbohydrate Chains

Cited by 8 publications

References 199 publications

Characterization of the N-linked oligosaccharides from human chorionic gonadotropin expressed in the methylotrophic yeast Pichia pastoris

Characterization of the N-linked oligosaccharides from human chorionic gonadotropin expressed in the methylotrophic yeast Pichia pastoris

Thyroid-Stimulating Hormone and Thyroid-Stimulating Hormone Receptor Structure-Function Relationships

Structure/function of N ‐glycans

Contact Info

Product

Resources

About