-
Glycoconjugate Journal Jun 2016Glycosylation is the most abundant and complex protein modification, and can have a profound structural and functional effect on the conjugate. The oligosaccharide... (Review)
Review
Glycosylation is the most abundant and complex protein modification, and can have a profound structural and functional effect on the conjugate. The oligosaccharide fraction is recognized to be involved in multiple biological processes, and to affect proteins physical properties, and has consequentially been labeled a critical quality attribute of biopharmaceuticals. Additionally, due to recent advances in analytical methods and analysis software, glycosylation is targeted in the search for disease biomarkers for early diagnosis and patient stratification. Biofluids such as saliva, serum or plasma are of great use in this regard, as they are easily accessible and can provide relevant glycosylation information. Thus, as the assessment of protein glycosylation is becoming a major element in clinical and biopharmaceutical research, this review aims to convey the current state of knowledge on the N-glycosylation of the major plasma glycoproteins alpha-1-acid glycoprotein, alpha-1-antitrypsin, alpha-1B-glycoprotein, alpha-2-HS-glycoprotein, alpha-2-macroglobulin, antithrombin-III, apolipoprotein B-100, apolipoprotein D, apolipoprotein F, beta-2-glycoprotein 1, ceruloplasmin, fibrinogen, immunoglobulin (Ig) A, IgG, IgM, haptoglobin, hemopexin, histidine-rich glycoprotein, kininogen-1, serotransferrin, vitronectin, and zinc-alpha-2-glycoprotein. In addition, the less abundant immunoglobulins D and E are included because of their major relevance in immunology and biopharmaceutical research. Where available, the glycosylation is described in a site-specific manner. In the discussion, we put the glycosylation of individual proteins into perspective and speculate how the individual proteins may contribute to a total plasma N-glycosylation profile determined at the released glycan level.
Topics: Blood Proteins; Glycoproteins; Glycosylation; Humans; Protein Processing, Post-Translational
PubMed: 26555091
DOI: 10.1007/s10719-015-9626-2 -
Cardiovascular Research Mar 2021Protein glycosylation is a post-translational modification consisting in the enzymatic attachment of carbohydrate chains to specific residues of the protein sequence.... (Review)
Review
Protein glycosylation is a post-translational modification consisting in the enzymatic attachment of carbohydrate chains to specific residues of the protein sequence. Several types of glycosylation have been described, with N-glycosylation and O-glycosylation being the most common types impacting on crucial biological processes, such as protein synthesis, trafficking, localization, and function. Genetic defects in genes involved in protein glycosylation may result in altered production and activity of several proteins, with a broad range of clinical manifestations, including dyslipidaemia and atherosclerosis. A large number of apolipoproteins, lipoprotein receptors, and other proteins involved in lipoprotein metabolism are glycosylated, and alterations in their glycosylation profile are associated with changes in their expression and/or function. Rare genetic diseases and population genetics have provided additional information linking protein glycosylation to the regulation of lipoprotein metabolism.
Topics: Animals; Apolipoproteins; Atherosclerosis; Dyslipidemias; Genetic Predisposition to Disease; Glycosylation; Humans; Lipid Metabolism; Lipoproteins; Phenotype; Plaque, Atherosclerotic; Protein Processing, Post-Translational; Receptors, Lipoprotein
PubMed: 32886765
DOI: 10.1093/cvr/cvaa252 -
Biotechnology Advances Sep 2023Glycosylation-mediated post-translational modification is critical for regulating many fundamental processes like cell division, differentiation, immune response, and... (Review)
Review
Glycosylation-mediated post-translational modification is critical for regulating many fundamental processes like cell division, differentiation, immune response, and cell-to-cell interaction. Alterations in the N-linked or O-linked glycosylation pattern of regulatory proteins like transcription factors or cellular receptors lead to many diseases, including cancer. These alterations give rise to micro- and macro-heterogeneity in tumor cells. Here, we review the role of O- and N-linked glycosylation and its regulatory function in autoimmunity and aberrant glycosylation in cancer. The change in cellular glycome could result from a change in the expression of glycosidases or glycosyltransferases like N-acetyl-glucosaminyl transferase V, FUT8, ST6Gal-I, DPAGT1, etc., impact the glycosylation of target proteins leading to transformation. Moreover, the mutations in glycogenes affect glycosylation patterns on immune cells leading to other related manifestations like pro- or anti-inflammatory effects. In recent years, understanding the glycome to cancer indicates that it can be utilized for both diagnosis/prognosis as well as immunotherapy. Studies involving mass spectrometry of proteome, site- and structure-specific glycoproteomics, or transcriptomics/genomics of patient samples and cancer models revealed the importance of glycosylation homeostasis in cancer biology. The development of emerging technologies, such as the lectin microarray, has facilitated research on the structure and function of glycans and glycosylation. Newly developed devices allow for high-throughput, high-speed, and precise research on aberrant glycosylation. This paper also discusses emerging technologies and clinical applications of glycosylation.
Topics: Humans; Glycosylation; Neoplasms; Glycosyltransferases; Lectins; Immunotherapy; Polysaccharides
PubMed: 37030554
DOI: 10.1016/j.biotechadv.2023.108149 -
Current Opinion in Neurobiology Feb 2022Despite being caused by a single protein, prion diseases are strikingly heterogenous. Individual prion variants, known as strains, possess distinct biochemical... (Review)
Review
Despite being caused by a single protein, prion diseases are strikingly heterogenous. Individual prion variants, known as strains, possess distinct biochemical properties, form aggregates with characteristic morphologies and preferentially seed certain brain regions, causing markedly different disease phenotypes. Strain diversity is determined by protein structure, post-translational modifications and the presence of extracellular matrix components, with single amino acid substitutions or altered protein glycosylation exerting dramatic effects. Here, we review recent advances in the study of prion strains and discuss how a deeper knowledge of the molecular origins of strain heterogeneity is providing a foundation for the development of anti-prion therapeutics.
Topics: Brain; Glycosylation; Humans; Phenotype; Prion Diseases; Prions
PubMed: 34416480
DOI: 10.1016/j.conb.2021.07.010 -
Organic & Biomolecular Chemistry Aug 2022Protein glycosylation is a key post-translational modification important to many facets of biology. Glycosylation can have critical effects on protein conformation,... (Review)
Review
Protein glycosylation is a key post-translational modification important to many facets of biology. Glycosylation can have critical effects on protein conformation, uptake and intracellular routing. In immunology, glycosylation of antigens has been shown to play a role in self/non-self distinction and the effective uptake of antigens. Improperly glycosylated proteins and peptide fragments, for instance those produced by cancerous cells, are also prime candidates for vaccine design. To study these processes, access to peptides bearing well-defined glycans is of critical importance. In this review, the key approaches towards synthetic, well-defined glycopeptides, are described, with a focus on peptides useful for and used in immunological studies. Special attention is given to the glycoconjugation approaches that have been developed in recent years, as these enable rapid synthesis of various (unnatural) glycopeptides, enabling powerful carbohydrate structure/activity studies. These techniques, combined with more traditional total synthesis and chemoenzymatic methods for the production of glycopeptides, should help unravel some of the complexities of glycobiology in the near future.
Topics: Glycomics; Glycopeptides; Glycosylation; Peptides; Polysaccharides
PubMed: 35903971
DOI: 10.1039/d2ob00829g -
Electrophoresis Dec 2018Protein glycosylation, an important PTM, plays an essential role in a wide range of biological processes such as immune response, intercellular signaling, inflammation,... (Review)
Review
Protein glycosylation, an important PTM, plays an essential role in a wide range of biological processes such as immune response, intercellular signaling, inflammation, and host-pathogen interaction. Aberrant glycosylation has been correlated with various diseases. However, studying protein glycosylation remains challenging because of low abundance, microheterogeneities of glycosylation sites, and poor ionization efficiency of glycopeptides. Therefore, the development of sensitive and accurate approaches to characterize protein glycosylation is crucial. The identification and characterization of protein glycosylation by MS is referred to as the field of glycoproteomics. Methods such as enrichment, metabolic labeling, and derivatization of glycopeptides in conjunction with different MS techniques and bioinformatics tools, have been developed to achieve an unequivocal quantitative and qualitative characterization of glycoproteins. This review summarizes the recent developments in the field of glycoproteomics over the past 6 years (2012 to 2018).
Topics: Animals; Glycopeptides; Glycoproteins; Glycosylation; Humans; Mass Spectrometry; Mice; Proteomics
PubMed: 30203847
DOI: 10.1002/elps.201800272 -
Viruses Jul 2022The papers published in this Special Issue include various essential steps and regulatory mechanisms involved in viral protein synthesis, protein processing,...
The papers published in this Special Issue include various essential steps and regulatory mechanisms involved in viral protein synthesis, protein processing, glycosylation, and assembly [...].
Topics: Glycosylation; Protein Processing, Post-Translational; Viral Proteins
PubMed: 36016272
DOI: 10.3390/v14081650 -
Ageing Research Reviews Aug 2023Glycosylation is a common post-translational modification of brain proteins including cell surface adhesion molecules, synaptic proteins, receptors and channels, as well... (Review)
Review
Glycosylation is a common post-translational modification of brain proteins including cell surface adhesion molecules, synaptic proteins, receptors and channels, as well as intracellular proteins, with implications in brain development and functions. Using advanced state-of-the-art glycomics and glycoproteomics technologies in conjunction with glycoinformatics resources, characteristic glycosylation profiles in brain tissues are increasingly reported in the literature and growing evidence shows deregulation of glycosylation in central nervous system disorders, including aging associated neurodegenerative diseases. Glycan signatures characteristic of brain tissue are also frequently described in cerebrospinal fluid due to its enrichment in brain-derived molecules. A detailed structural analysis of brain and cerebrospinal fluid glycans collected in publications in healthy and neurodegenerative conditions was undertaken and data was compiled to create a browsable dedicated set in the GlyConnect database of glycoproteins (https://glyconnect.expasy.org/brain). The shared molecular composition of cerebrospinal fluid with brain enhances the likelihood of novel glycobiomarker discovery for neurodegeneration, which may aid in unveiling disease mechanisms, therefore, providing with novel therapeutic targets as well as diagnostic and progression monitoring tools.
Topics: Humans; Glycosylation; Neurodegenerative Diseases; Glycoproteins; Protein Processing, Post-Translational; Glycomics; Polysaccharides; Biomarkers
PubMed: 37348818
DOI: 10.1016/j.arr.2023.101991 -
Bioscience Reports Oct 2022Protein glycosylation is ubiquitous throughout biology. From bacteria to humans, this post translational modification with sophisticated carbohydrate structures plays a... (Review)
Review
Protein glycosylation is ubiquitous throughout biology. From bacteria to humans, this post translational modification with sophisticated carbohydrate structures plays a profound role in the interaction of proteins with cells and changes the physiochemical properties of the proteins that carry them. When the glycans are linked to Ser or Thr residues, they are known as O-linked glycans, as the glycosidic linkage is through oxygen. O-glycans are perhaps best known as part of the mucin proteins, however many soluble proteins carry these types of glycans, and that their roles in biology are still being discovered. Many of the soluble proteins that carry O-glycans have a role as therapeutic proteins, and in the 21st century, the application of synthetic biology is starting to be applied to improving these proteins through manipulation of the glycans. This review will explore the role of these O-linked glycans in proteins with pharmaceutical significance, as well as recent advancements in recombinant glycoprotein therapeutics.
Topics: Humans; Glycosylation; Polysaccharides; Mucins; Protein Processing, Post-Translational; Recombinant Proteins
PubMed: 36214107
DOI: 10.1042/BSR20220094 -
Oncogene Jun 2023Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. Understanding the cancer mechanisms provides novel diagnostic, prognostic, and... (Review)
Review
Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. Understanding the cancer mechanisms provides novel diagnostic, prognostic, and therapeutic markers for the management of HCC disease. In addition to genomic and epigenomic regulation, post-translational modification exerts a profound influence on protein functions and plays a critical role in regulating various biological processes. Protein glycosylation is one of the most common and complex post-translational modifications of newly synthesized proteins and acts as an important regulatory mechanism that is implicated in fundamental molecular and cell biology processes. Recent studies in glycobiology suggest that aberrant protein glycosylation in hepatocytes contributes to the malignant transformation to HCC by modulating a wide range of pro-tumorigenic signaling pathways. The dysregulated protein glycosylation regulates cancer growth, metastasis, stemness, immune evasion, and therapy resistance, and is regarded as a hallmark of HCC. Changes in protein glycosylation could serve as potential diagnostic, prognostic, and therapeutic factors in HCC. In this review, we summarize the functional importance, molecular mechanism, and clinical application of protein glycosylation alterations in HCC.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Glycosylation; Protein Processing, Post-Translational; Carcinogenesis; Proteins
PubMed: 37193819
DOI: 10.1038/s41388-023-02702-w