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Advances in Experimental Medicine and... 2021Expression of glycosylation-related genes (or glycogenes) is strictly regulated by transcription factors and epigenetic processes, both in normal and in pathological...
Expression of glycosylation-related genes (or glycogenes) is strictly regulated by transcription factors and epigenetic processes, both in normal and in pathological conditions. In fact, glycosylation is an essential mechanism through which proteins and lipids are modified to perform a variety of biological events, to adapt to environment, and to interact with microorganisms.Many glycogenes with a role in normal development are epigenetically regulated. Essential studies were performed in the brain, where expression of glycogenes like MGAT5B, B4GALNT1, and ST8Sia1 are under the control of histone modifications, and in the immune system, where expression of FUT7 is regulated by both DNA methylation and histone modifications. At present, epigenetic regulation of glycosylation is still poorly described under physiological conditions, since the majority of the studies were focused on cancer. In fact, virtually all types of cancers display aberrant glycosylation, because of both genetic and epigenetic modifications on glycogenes. This is also true for many other diseases, such as inflammatory bowel disease, diabetes, systemic lupus erythematosus, IgA nephropathy, multiple sclerosis, and cardiovascular diseases.A deeper knowledge in epigenetic regulation of glycogenes is essential, since research in this field could be helpful in finding novel and personalized therapeutics.
Topics: DNA Methylation; Epigenesis, Genetic; Glycosylation; Histone Code; Protein Processing, Post-Translational
PubMed: 34495535
DOI: 10.1007/978-3-030-70115-4_8 -
Electrophoresis Jan 2022Protein glycosylation is one of the most common posttranslational modifications, and plays an essential role in a wide range of biological processes such as immune... (Review)
Review
Protein glycosylation is one of the most common posttranslational modifications, and plays an essential role in a wide range of biological processes such as immune response, intercellular signaling, inflammation, host-pathogen interaction, and protein stability. Glycoproteomics is a proteomics subfield dedicated to identifying and characterizing the glycans and glycoproteins in a given cell or tissue. Aberrant glycosylation has been associated with various diseases such as Alzheimer's disease, viral infections, inflammation, immune deficiencies, congenital disorders, and cancers. However, glycoproteomic analysis remains challenging because of the low abundance, site-specific heterogeneity, and poor ionization efficiency of glycopeptides during LC-MS analyses. Therefore, the development of sensitive and accurate approaches to efficiently characterize protein glycosylation is crucial. Methods such as metabolic labeling, enrichment, and derivatization of glycopeptides, coupled with different mass spectrometry techniques and bioinformatics tools, have been developed to achieve sophisticated levels of quantitative and qualitative analyses of glycoproteins. This review attempts to update the recent developments in the field of glycoproteomics reported between 2017 and 2021.
Topics: Chromatography, Liquid; Glycopeptides; Glycosylation; Mass Spectrometry; Proteomics
PubMed: 34614238
DOI: 10.1002/elps.202100188 -
Proteomics Aug 2022Glycosylation of viral proteins is required for the progeny formation and infectivity of virtually all viruses. It is increasingly clear that distinct glycans also play... (Review)
Review
Glycosylation of viral proteins is required for the progeny formation and infectivity of virtually all viruses. It is increasingly clear that distinct glycans also play pivotal roles in the virus's ability to shield and evade the host's immune system. Recently, there has been a great advancement in structural identification and quantitation of viral glycosylation, especially spike proteins. Given the ongoing pandemic and the high demand for structure analysis of SARS-CoV-2 densely glycosylated spike protein, mass spectrometry methodologies have been employed to accurately determine glycosylation patterns. There are still many challenges in the determination of site-specific glycosylation of SARS-CoV-2 viral spike protein. This is compounded by some conflicting results regarding glycan site occupancy and glycan structural characterization. These are probably due to differences in the expression systems, form of expressed spike glycoprotein, MS methodologies, and analysis software. In this review, we recap the glycosylation of spike protein and compare among various studies. Also, we describe the most recent advancements in glycosylation analysis in greater detail and we explain some misinterpretation of previously observed data in recent publications. Our study provides a comprehensive view of the spike protein glycosylation and highlights the importance of consistent glycosylation determination.
Topics: COVID-19; Glycosylation; Humans; Mass Spectrometry; Polysaccharides; SARS-CoV-2; Spike Glycoprotein, Coronavirus
PubMed: 35700310
DOI: 10.1002/pmic.202100322 -
Cells Aug 2020The protein glycosylation is a post-translational modification of crucial importance for its involvement in molecular recognition, protein trafficking, regulation, and... (Review)
Review
The protein glycosylation is a post-translational modification of crucial importance for its involvement in molecular recognition, protein trafficking, regulation, and inflammation. Indeed, abnormalities in protein glycosylation are correlated with several disease states such as cancer, inflammatory diseases, and congenial disorders. The understanding of cellular mechanisms through the elucidation of glycan composition encourages researchers to find analytical solutions for their detection. Actually, the multiplicity and diversity of glycan structures bond to the proteins, the variations in polarity of the individual saccharide residues, and the poor ionization efficiencies make their detection much trickier than other kinds of biopolymers. An overview of the most prominent techniques based on mass spectrometry (MS) for protein glycosylation (glycoproteomics) studies is here presented. The tricks and pre-treatments of samples are discussed as a crucial step prodromal to the MS analysis to improve the glycan ionization efficiency. Therefore, the different instrumental MS mode is also explored for the qualitative and quantitative analysis of glycopeptides and the glycans structural composition, thus contributing to the elucidation of biological mechanisms.
Topics: Glycosylation; Humans; Mass Spectrometry; Protein Processing, Post-Translational; Proteomics
PubMed: 32872358
DOI: 10.3390/cells9091986 -
Molecular Biology Reports Aug 2022As a post-translational modification, glycosylation plays vital role in regulating the folding and function of proteins necessary for many biological processes. Unlike... (Review)
Review
INTRODUCTION
As a post-translational modification, glycosylation plays vital role in regulating the folding and function of proteins necessary for many biological processes. Unlike glycation, glycosylation is an enzymatic process; glycosyltransferases transfer sugars to proteins, forming glycosidic bonds with amino acid residues on proteins. Changes that interfere with the enzymatic reaction and result in abnormal glycosylation can spatio-temporally affect the balance of glycosylation, leading to disease states. Muscle diseases have been associated with dysfunctional protein glycosylation, and many studies have focused on the pathophysiology underlying this association. This review aims to summarize the research progress on protein glycosylation in the pathogenesis of muscle diseases and provides new insight into the muscle research field.
METHODS
Literatures were reviewed comparatively and data were organized to find information about protein glycosylation and its role in muscle disease.
RESULTS
Protein glycosylation modification is closely related to the occurrence of muscle diseases. α-DG is a key protein in the study of inherited muscle diseases and has a wide range of glycosylation, including O-linked glycosylation and N-linked glycosylation. Besides, O-GlcNAc glycosylation is an important mechanism of protein glycosylation, helping maintaining the structure and function of skeletal muscle and participating in multiple biological processes. Protein glycosylation is also connected to muscle disease and neurodegenerative diseases, especially Alzheimer's disease.
CONCLUSIONS
Taken together, better understanding of protein glycosylation and its implication in muscle disease would help provide new perspectives in the prevention and treatment measures for human muscle diseases.
Topics: Glycosylation; Humans; Muscle, Skeletal; Muscular Diseases; Protein Processing, Post-Translational; Proteins
PubMed: 35428929
DOI: 10.1007/s11033-022-07334-z -
Molecular & Cellular Proteomics : MCP 2021Mass spectrometry-based glycoproteomics has gone through some incredible developments over the last few years. Technological advances in glycopeptide enrichment,... (Review)
Review
Mass spectrometry-based glycoproteomics has gone through some incredible developments over the last few years. Technological advances in glycopeptide enrichment, fragmentation methods, and data analysis workflows have enabled the transition of glycoproteomics from a niche application, mainly focused on the characterization of isolated glycoproteins, to a mature technology capable of profiling thousands of intact glycopeptides at once. In addition to numerous biological discoveries catalyzed by the technology, we are also observing an increase in studies focusing on global protein glycosylation and the relationship between multiple glycosylation sites on the same protein. It has become apparent that just describing protein glycosylation in terms of micro- and macro-heterogeneity, respectively, the variation and occupancy of glycans at a given site, is not sufficient to describe the observed interactions between sites. In this perspective we propose a new term, meta-heterogeneity, to describe a higher level of glycan regulation: the variation in glycosylation across multiple sites of a given protein. We provide literature examples of extensive meta-heterogeneity on relevant proteins such as antibodies, erythropoietin, myeloperoxidase, and a number of serum and plasma proteins. Furthermore, we postulate on the possible biological reasons and causes behind the intriguing meta-heterogeneity observed in glycoproteins.
Topics: Animals; Glycoproteins; Glycosylation; Humans; Software
PubMed: 33561609
DOI: 10.1074/mcp.R120.002093 -
Carbohydrate Research Apr 2022Monoclonal antibodies (mAbs) are amazingly successful in treating diseases such as various types of cancers, immune disorders, and infections. Currently, mAbs are... (Review)
Review
Monoclonal antibodies (mAbs) are amazingly successful in treating diseases such as various types of cancers, immune disorders, and infections. Currently, mAbs are considered the most versatile therapeutic available. Seminal scientific progress over the last decade on elucidating the functional role of antibody N-glycosylation revealed the significance of this post-translational modification on the stability, half-life, and biological activity of antibodies. Therefore, antibody N-glycosylation became a key aspect of biopharmaceutical mAb production in large-scale manufacturing processes. This Mini-Review summarizes the recent scientific attempts of producing mAbs in glycoengineered animal-, plant-, and yeast cell lines. Furthermore, we also describe novel approaches for analyzing mAb N-glycosylation.
Topics: Animals; Antibodies, Monoclonal; Biotechnology; Glycosylation; Neoplasms; Protein Processing, Post-Translational
PubMed: 35344785
DOI: 10.1016/j.carres.2022.108541 -
Molecular Biology Reports Aug 2022N-linked protein glycosylation is an essential co-and posttranslational protein modification that occurs in all three domains of life; the assembly of N-glycans follows... (Review)
Review
N-linked protein glycosylation is an essential co-and posttranslational protein modification that occurs in all three domains of life; the assembly of N-glycans follows a complex sequence of events spanning the (Endoplasmic Reticulum) ER and the Golgi apparatus. It has a significant impact on both physicochemical properties and biological functions. It plays a significant role in protein folding and quality control, glycoprotein interaction, signal transduction, viral attachment, and immune response to infection. Glycoengineering of protein employed for improving protein properties and plays a vital role in the production of recombinant glycoproteins and struggles to humanize recombinant therapeutic proteins. It considers an alternative platform for biopharmaceuticals production. Many immune proteins and antibodies are glycosylated. Pathogen's glycoproteins play vital roles during the infection cycle and their expression of specific oligosaccharides via the N-glycosylation pathway to evade detection by the host immune system. This review focuses on the aspects of N-glycosylation processing, glycoengineering approaches, their role in viral attachment, and immune responses to infection.
Topics: Endoplasmic Reticulum; Glycoproteins; Glycosylation; Golgi Apparatus; Humans; Polysaccharides; Recombinant Proteins; Virus Diseases
PubMed: 35364718
DOI: 10.1007/s11033-022-07359-4 -
Biotechnology Advances 2024A key aspect of successful viral vaccine design is the elicitation of neutralizing antibodies targeting viral attachment and fusion glycoproteins that embellish viral... (Review)
Review
A key aspect of successful viral vaccine design is the elicitation of neutralizing antibodies targeting viral attachment and fusion glycoproteins that embellish viral particles. This observation has catalyzed the development of numerous viral glycoprotein mimetics as vaccines. Glycans can dominate the surface of viral glycoproteins and as such, the viral glycome can influence the antigenicity and immunogenicity of a candidate vaccine. In one extreme, glycans can form an integral part of epitopes targeted by neutralizing antibodies and are therefore considered to be an important feature of key immunogens within an immunization regimen. In the other extreme, the existence of peptide and bacterially expressed protein vaccines shows that viral glycosylation can be dispensable in some cases. However, native-like glycosylation can indicate native-like protein folding and the presence of conformational epitopes. Furthermore, going beyond native glycan mimicry, in either occupancy of glycosylation sites or the glycan processing state, may offer opportunities for enhancing the immunogenicity and associated protection elicited by an immunogen. Here, we review key determinants of viral glycosylation and how recombinant immunogens can recapitulate these signatures across a range of enveloped viruses, including HIV-1, Ebola virus, SARS-CoV-2, Influenza and Lassa virus. The emerging understanding of immunogen glycosylation and its control will help guide the development of future vaccines in both recombinant protein- and nucleic acid-based vaccine technologies.
Topics: Glycosylation; Glycoproteins; Antibodies, Neutralizing; Epitopes; Vaccines; Polysaccharides
PubMed: 37972669
DOI: 10.1016/j.biotechadv.2023.108283 -
Expert Review of Proteomics 2023Hepatocellular carcinoma (HCC) represents a significant burden globally, which ranks sixth among the most frequently diagnosed cancers and stands as the third leading... (Review)
Review
INTRODUCTION
Hepatocellular carcinoma (HCC) represents a significant burden globally, which ranks sixth among the most frequently diagnosed cancers and stands as the third leading cause of cancer-related mortality. Glycoproteomics, as an important branch of proteomics, has already made significant achievements in the field of HCC research. Aberrant protein glycosylation has shown to promote the malignant transformation of hepatocytes by modulating a wide range of tumor-promoting signaling pathways. The glycoproteome provides valuable information for understanding cancer progression, tumor immunity, and clinical outcome, which could serve as potential diagnostic, prognostic, and therapeutic tools in HCC.
AREAS COVERED
In this review, recent advances of glycoproteomics contribute to clinical applications (diagnosis and prognosis) and molecular mechanisms (hepatocarcinogenesis, progression, stemness and recurrence, and drug resistance) of HCC are summarized.
EXPERT OPINION
Glycoproteomics shows promise in HCC, enhancing early detection, risk stratification, and personalized treatments. Challenges include sample heterogeneity, diverse glycans structures, sensitivity issues, complex workflows, limited databases, and incomplete understanding of immune cell glycosylation. Addressing these limitations requires collaborative efforts, technological advancements, standardization, and validation studies. Future research should focus on targeting abnormal protein glycosylation therapeutically. Advancements in glycobiomarkers and glycosylation-targeted therapies will greatly impact HCC diagnosis, prognosis, and treatment.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Glycoproteins; Glycosylation; Polysaccharides
PubMed: 37882248
DOI: 10.1080/14789450.2023.2265064