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Advances in Experimental Medicine and... 2023De novo synthesis of dolichol (Dol) and dolichyl phosphate (Dol-P) is essential for protein glycosylation. Herein, we provide a brief overview of Dol and Dol-P synthesis... (Review)
Review
De novo synthesis of dolichol (Dol) and dolichyl phosphate (Dol-P) is essential for protein glycosylation. Herein, we provide a brief overview of Dol and Dol-P synthesis and the maintenance of their cellular content. Retinal Dol metabolism and the requirement of Dol-linked oligosaccharide synthesis in the neural retina also are discussed. There are recently discovered and an emerging class of rare congenital disorders that affect Dol metabolism, involving the genes DHDDS, NUS1, SRD5A3, and DOLK. Further understanding of these congenital disorders is evolving, based upon studies utilizing yeast and murine models, as well as clinical reports of these rare disorders. We summarize the known visual deficits associated with Dol metabolism disorders, and identify the need for generation and characterization of suitable animal models of these disorders to elucidate the underlying molecular and cellular mechanisms of the associated retinopathies.
Topics: Animals; Mice; Dolichols; Glycosylation; Oligosaccharides; Retina; Saccharomyces cerevisiae
PubMed: 37440071
DOI: 10.1007/978-3-031-27681-1_66 -
Angewandte Chemie (International Ed. in... May 2022Protein glycosylation plays critical roles in many biological processes. However, the fundamental study and application of glycobiology are hindered by the...
Protein glycosylation plays critical roles in many biological processes. However, the fundamental study and application of glycobiology are hindered by the heterogeneousness of oligosaccharides in natural glycoproteins and the difficulty in constructing glycoproteins of human design. Herein, we describe a semisynthetic method to site-specifically modify proteins with reducing carbohydrates. The method involves the genetic incorporation of a side-chain-esterified aspartate, which was subsequently quantitatively converted into alanine-β-hydrazide (Aβz), and chemoselective conjugation of Aβz with a range of readily available reducing carbohydrates. The resulting Aβz-linked GlcNAc is a close mimic of native N-GlcNAc and could be installed on various proteins, including IL-17A and RNase A. Notably, Aβz-linked GlcNAc on proteins reacted with biantennary oligosaccharide oxazoline derivatives through endoglycosidase-catalyzed transglycosylation reactions to enable the assembly of homogeneous glycans on proteins.
Topics: Glycoproteins; Glycosylation; Humans; Oligosaccharides; Polysaccharides; Protein Processing, Post-Translational
PubMed: 35225420
DOI: 10.1002/anie.202116545 -
Virulence Dec 2022Glycans are among the most important cell molecular components. However, given their structural diversity, their functions have not been fully explored. Glycosylation is... (Review)
Review
Glycans are among the most important cell molecular components. However, given their structural diversity, their functions have not been fully explored. Glycosylation is a vital post-translational modification for various proteins. Many bacteria and viruses rely on -linked and O-linked glycosylation to perform critical biological functions. The diverse functions of glycosylation on viral proteins during viral infections, including Dengue, Zika, influenza, and human immunodeficiency viruses as well as coronaviruses have been reported. -linked glycosylation is the most common form of protein modification, and it modulates folding, transportation and receptor binding. Compared to -linked glycosylation, the functions of O-linked viral protein glycosylation have not been comprehensively evaluated. In this review, we summarize findings on viral protein glycosylation, with particular attention to studies on N-linked glycosylation in viral life cycles. This review informs the development of virus-specific vaccines or inhibitors.
Topics: Glycosylation; Host Microbial Interactions; Humans; Protein Processing, Post-Translational; Viral Proteins; Virulence; Zika Virus; Zika Virus Infection
PubMed: 35436420
DOI: 10.1080/21505594.2022.2060464 -
Trends in Molecular Medicine Apr 2022The importance of glycosylation (post-translational attachment of glycan residues to proteins) in the context of neuroinflammation is only now beginning to be... (Review)
Review
The importance of glycosylation (post-translational attachment of glycan residues to proteins) in the context of neuroinflammation is only now beginning to be understood. Although the glycome is challenging to investigate due to its complexity, this field is gaining interest because of the emergence of novel analytical methods. These investigations offer the possibility of further understanding the molecular signature of disorders with underlying neuroinflammatory cascades. In this review, we portray the clinically relevant trends in glyconeurobiology and suggest glyco-related paths that could be targeted therapeutically to decrease neuroinflammation. A combinatorial insight from glycobiology and neurology can be harnessed to better understand neuroinflammatory-related conditions to identify relevant molecular targets.
Topics: Glycosylation; Humans; Neuroinflammatory Diseases; Polysaccharides; Protein Processing, Post-Translational
PubMed: 35120836
DOI: 10.1016/j.molmed.2022.01.004 -
Advances in Experimental Medicine and... 2021Glycosylation plays an important role in infectious diseases. Many important interactions between pathogens and hosts involve their carbohydrate structures (glycans).... (Review)
Review
Glycosylation plays an important role in infectious diseases. Many important interactions between pathogens and hosts involve their carbohydrate structures (glycans). Glycan interactions can mediate adhesion, recognition, invasion, and immune evasion of pathogens. To date, changes in many protein N/O-linked glycosylation have been identified as biomarkers for the development of infectious diseases and cancers. In this review, we will discuss the principal findings and the roles of glycosylation of both pathogens and host cells in the context of human important infectious diseases. Understanding the role and mechanism of glycan-lectin interaction between pathogens and hosts may create a new paradigm for discovering novel glycan-based therapies that can lead to eradication or functional cure of pathogens infection.
Topics: Communicable Diseases; Glycosylation; Humans; Immune Evasion; Lectins; Polysaccharides
PubMed: 34495538
DOI: 10.1007/978-3-030-70115-4_11 -
The New Phytologist May 2021Glycosylation is a conserved set of post-translational modifications that exists in all eukaryotic cells. During the last decade, the role of glycosylation in plant... (Review)
Review
Glycosylation is a conserved set of post-translational modifications that exists in all eukaryotic cells. During the last decade, the role of glycosylation in plant pathogenic fungi has received significant attention and considerable progress has been made especially in Ustilago maydis and Magnaporthe oryzae. Here, we review recent advances in our understanding of the role of N-glycosylation, O-glycosylation and glycosylphosphatidylinositol (GPI) anchors during plant infection by pathogenic fungi. We highlight the roles of these processes in regulatory mechanisms associated with appressorium formation, host penetration, biotrophic growth and immune evasion. We argue that improved knowledge of glycosylation pathways and the impact of these modifications on fungal pathogenesis is overdue and could provide novel strategies for disease control.
Topics: Ascomycota; Basidiomycota; Fungal Proteins; Glycosylation; Magnaporthe; Oryza; Plant Diseases; Virulence
PubMed: 33454977
DOI: 10.1111/nph.17207 -
Biotechnology Advances Oct 2023In order to meet the rising demand for biologics and become competitive on the developing biosimilar market, there is a need for process intensification of... (Review)
Review
In order to meet the rising demand for biologics and become competitive on the developing biosimilar market, there is a need for process intensification of biomanufacturing processes. Process development of biologics has historically relied on extensive experimentation to develop and optimize biopharmaceutical manufacturing. Experimentation to optimize media formulations, feeding schedules, bioreactor operations and bioreactor scale up is expensive, labor intensive and time consuming. Mathematical modeling frameworks have the potential to enable process intensification while reducing the experimental burden. This review focuses on mathematical modeling of cellular metabolism and N-linked glycosylation as applied to upstream manufacturing of biologics. We review developments in the field of modeling cellular metabolism of mammalian cells using kinetic and stoichiometric modeling frameworks along with their applications to simulate, optimize and improve mechanistic understanding of the process. Interest in modeling N-linked glycosylation has led to the creation of various types of parametric and non-parametric models. Most published studies on mammalian cell metabolism have performed experiments in shake flasks where the pH and dissolved oxygen cannot be controlled. Efforts to understand and model the effect of bioreactor-specific parameters such as pH, dissolved oxygen, temperature, and bioreactor heterogeneity are critically reviewed. Most modeling efforts have focused on the Chinese Hamster Ovary (CHO) cells, which are most commonly used to produce monoclonal antibodies (mAbs). However, these modeling approaches can be generalized and applied to any mammalian cell-based manufacturing platform. Current and potential future applications of these models for Vero cell-based vaccine manufacturing, CAR-T cell therapies, and viral vector manufacturing are also discussed. We offer specific recommendations for improving the applicability of these models to industrially relevant processes.
Topics: Cricetinae; Animals; Glycosylation; Cricetulus; CHO Cells; Cell Culture Techniques; Bioreactors; Biological Products
PubMed: 37257729
DOI: 10.1016/j.biotechadv.2023.108179 -
Gastroenterology Jan 2020Glycans are sequences of carbohydrates that are added to proteins or lipids to modulate their structure and function. Glycans modify proteins required for regulation of... (Review)
Review
Glycans are sequences of carbohydrates that are added to proteins or lipids to modulate their structure and function. Glycans modify proteins required for regulation of immune cells, and alterations have been associated with inflammatory conditions. For example, specific glycans regulate T-cell activation, structures, and functions of immunoglobulins; interactions between microbes and immune and epithelial cells; and malignant transformation in the intestine and liver. We review the effects of protein glycosylation in regulation of gastrointestinal and liver functions, and how alterations in glycosylation serve as diagnostic or prognostic factors, or as targets for therapy.
Topics: Biomarkers; Gastrointestinal Diseases; Gastrointestinal Tract; Glycomics; Glycosylation; Humans; Liver; Liver Diseases; Polysaccharides; Prognosis; Proteomics; T-Lymphocytes; Time Factors
PubMed: 31626754
DOI: 10.1053/j.gastro.2019.08.060 -
Seminars in Cancer Biology Jun 2017Although altered glycosylation has been detected in human cancer cells decades ago, only investigations in the last years have enormously increased our knowledge about... (Review)
Review
Although altered glycosylation has been detected in human cancer cells decades ago, only investigations in the last years have enormously increased our knowledge about the details of protein glycosylation and its role in tumour progression. Many proteins, which are heavily glycosylated, i.e. adhesion proteins or proteases, play an important role in cancer metastasis that represents the crucial and frequently life-threatening step in progression of most tumour types. Compared to normal tissue, tumour cells often show altered glycosylation patters with appearance of new tumour-specific antigens. In this review, we give an overview about the role of glycosylation in tumour metastasis, describing recent results about O-glycans, N-glycans and glycosaminoglycans. We show that glycan structures, glycosylated proteins and glycosylation enzymes have influence on different steps of the metastatic process, including epithelial-mesenchymal transition (EMT), migration, invasion/intravasation and extravasation of tumour cells. Regarding the important role of cancer metastasis for patients survival, further knowledge about the consequences of altered glycosylation patterns in tumour cells is needed which might eventually lead to the development of novel therapeutic approaches.
Topics: Disease Progression; Epithelial-Mesenchymal Transition; Gene Expression Regulation, Neoplastic; Glycosylation; Humans; Neoplasm Metastasis; Neoplasm Proteins; Neoplasms; Protein Processing, Post-Translational
PubMed: 28315783
DOI: 10.1016/j.semcancer.2017.03.002 -
Biochemistry Mar 2017Protein glycosylation (N- and O-linked) plays an important role in many biological processes, including protein structure and function. However, the structural... (Review)
Review
Protein glycosylation (N- and O-linked) plays an important role in many biological processes, including protein structure and function. However, the structural elucidation of glycans, specifically O-linked glycans, remains a major challenge and is often overlooked during protein analysis. Recently, mass spectrometry (MS) has matured as a powerful technology for high-quality analytical characterization of O-linked glycans. This review summarizes the recent developments and insights of MS-based glycomics technologies, with a focus on mucin-type O-glycan analysis. Three main MS-based approaches are outlined: O-glycan profiling (structural analysis of released O-glycan), a "bottom-up" approach (analysis of an O-glycan covalently attached to a glycopeptide), and a "top-down" approach (analysis of a glycan attached to an intact glycoprotein). In addition, the most widely used MS ionization techniques, i.e., matrix-assisted laser desorption ionization and electrospray ionization, as well as ion activation techniques like collision-induced dissociation, electron capture dissociation, and electron transfer dissociation during O-glycan analysis are discussed. The MS technical approaches mentioned above are already major improvements for studying O-linked glycosylation and appear to be valuable for in-depth analysis of the type of O-glycan attached, branching patterns, and the occupancy of O-glycosylation sites.
Topics: Animals; Computational Biology; Glycoproteins; Glycosylation; Humans; Mass Spectrometry; Oxygen; Polysaccharides
PubMed: 28196325
DOI: 10.1021/acs.biochem.6b01244