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ChemistryOpen Mar 2020Many proteins in living organisms are glycosylated. As their glycan patterns exhibit protein-, cell-, and tissue-specific heterogeneity, changes in the glycosylation... (Review)
Review
Many proteins in living organisms are glycosylated. As their glycan patterns exhibit protein-, cell-, and tissue-specific heterogeneity, changes in the glycosylation levels could serve as useful indicators of various pathological and physiological states. Thus, the identification of glycoprotein biomarkers from specific changes in the glycan profiles of glycoproteins is a trending field. Lectin microarrays provide a new glycan analysis platform, which enables rapid and sensitive analysis of complex glycans without requiring the release of glycans from the protein. Recent developments in lectin microarray technology enable high-throughput analysis of glycans in complex biological samples. In this review, we will discuss the basic concepts and recent progress in lectin microarray technology, the application of lectin microarrays in biomarker discovery, and the challenges and future development of this technology. Given the tremendous technical advancements that have been made, lectin microarrays will become an indispensable tool for the discovery of glycoprotein biomarkers.
Topics: Biomarkers; Glycoproteins; Glycosylation; Humans; Lectins; Microarray Analysis; Polysaccharides; Protein Array Analysis; Protein Conformation
PubMed: 32154049
DOI: 10.1002/open.201900326 -
Proceedings of the National Academy of... Sep 2023Neutrophils store microbicidal glycoproteins in cytosolic granules to fight intruding pathogens, but their granule distribution and formation mechanism(s) during...
Neutrophils store microbicidal glycoproteins in cytosolic granules to fight intruding pathogens, but their granule distribution and formation mechanism(s) during granulopoiesis remain unmapped. Herein, we comprehensively profile the neutrophil -glycoproteome with spatiotemporal resolution by analyzing four key types of intracellular organelles isolated from blood-derived neutrophils and during their maturation from bone marrow-derived progenitors using a glycomics-guided glycoproteomics approach. Interestingly, the organelles of resting neutrophils exhibited distinctive glycophenotypes including, most strikingly, highly truncated -glycans low in α2,6-sialylation and Lewis fucosylation decorating a diverse set of microbicidal proteins (e.g., myeloperoxidase, azurocidin, neutrophil elastase) in the azurophilic granules. Excitingly, proteomics and transcriptomics data from discrete myeloid progenitor stages revealed that profound glycoproteome remodeling underpins the promyelocytic-to-metamyelocyte transition and that the glycophenotypic differences are driven primarily by dynamic changes in protein expression and less by changes within the glycosylation machinery. Notable exceptions were the oligosaccharyltransferase subunits responsible for initiation of -glycoprotein biosynthesis that were strongly expressed in early myeloid progenitors correlating with relatively high levels of glycosylation of the microbicidal proteins in the azurophilic granules. Our study provides spatiotemporal insights into the complex neutrophil -glycoproteome featuring intriguing organelle-specific -glycosylation patterns formed by dynamic glycoproteome remodeling during the early maturation stages of the myeloid progenitors.
Topics: Glycosylation; Neutrophils; Proteome; Cognition; Cytoplasmic Granules
PubMed: 37639587
DOI: 10.1073/pnas.2303867120 -
Cells Aug 2021Approximately thirty percent of the proteins synthesized in animal or plant cells travel through the secretory pathway. Seventy to eighty percent of those proteins are... (Review)
Review
Approximately thirty percent of the proteins synthesized in animal or plant cells travel through the secretory pathway. Seventy to eighty percent of those proteins are glycosylated. Thus, glycosylation is an important protein modification that is related to many cellular processes, such as differentiation, recognition, development, signal transduction, and immune response. Additionally, glycosylation affects protein folding, solubility, stability, biogenesis, and activity. Specifically, in plants, glycosylation has recently been related to the fruit ripening process. This review aims to provide valuable information and discuss the available literature focused on three principal topics: (I) glycosylations as a key posttranslational modification in development in plants, (II) experimental and bioinformatics tools to analyze glycosylations, and (III) a literature review related to glycosylations in fruit ripening. Based on these three topics, we propose that it is necessary to increase the number of studies related to posttranslational modifications, specifically protein glycosylation because the specific role of glycosylation in the posttranslational process and how this process affects normal fruit development and ripening remain unclear to date.
Topics: Computational Biology; Fruit; Gene Expression Regulation, Plant; Glycoproteins; Glycosylation; Plant Proteins; Protein Processing, Post-Translational; Seeds
PubMed: 34440864
DOI: 10.3390/cells10082095 -
Frontiers in Immunology 2023Immunoglobulin G (IgG) antibodies are a critical component of the adaptive immune system, binding to and neutralizing pathogens and other foreign substances. Recent... (Review)
Review
Immunoglobulin G (IgG) antibodies are a critical component of the adaptive immune system, binding to and neutralizing pathogens and other foreign substances. Recent advances in molecular antibody biology and structural protein engineering enabled the modification of IgG antibodies to enhance their therapeutic potential. This review summarizes recent progress in both natural and engineered structural modifications of IgG antibodies, including allotypic variation, glycosylation, Fc engineering, and Fc gamma receptor binding optimization. We discuss the functional consequences of these modifications to highlight their potential for therapeutical applications.
Topics: Immunoglobulin G; Receptors, IgG; Gamma Rays; Glycosylation; Molecular Biology
PubMed: 38259472
DOI: 10.3389/fimmu.2023.1304365 -
Mass Spectrometry Reviews Mar 2023Surface and secreted glycoproteins are essential to cells and regulate many extracellular events. Because of the diversity of glycans, the low abundance of many... (Review)
Review
Surface and secreted glycoproteins are essential to cells and regulate many extracellular events. Because of the diversity of glycans, the low abundance of many glycoproteins, and the complexity of biological samples, a system-wide investigation of extracellular glycoproteins is a daunting task. With the development of modern mass spectrometry (MS)-based proteomics, comprehensive analysis of different protein modifications including glycosylation has advanced dramatically. This review focuses on the investigation of extracellular glycoproteins using MS-based proteomics. We first discuss the methods for selectively enriching surface glycoproteins and investigating protein interactions on the cell surface, followed by the application of MS-based proteomics for surface glycoprotein dynamics analysis and biomarker discovery. We then summarize the methods to comprehensively study secreted glycoproteins by integrating various enrichment approaches with MS-based proteomics and their applications for global analysis of secreted glycoproteins in different biological samples. Collectively, MS significantly expands our knowledge of extracellular glycoproteins and enables us to identify extracellular glycoproteins as potential biomarkers for disease detection and drug targets for disease treatment.
Topics: Glycoproteins; Glycosylation; Mass Spectrometry; Protein Processing, Post-Translational; Proteomics
PubMed: 34047389
DOI: 10.1002/mas.21708 -
The Journal of Organic Chemistry Dec 2020The importance of post-translational glycosylation in protein structure and function has gained significant clinical relevance recently. The latest developments in...
The importance of post-translational glycosylation in protein structure and function has gained significant clinical relevance recently. The latest developments in glycobiology, glycochemistry, and glycoproteomics have made the field more manageable and relevant to disease progression and immune-response signaling. Here, we summarize the current progress in glycoscience, including the new methodologies that have led to the introduction of programmable and automatic as well as large-scale enzymatic synthesis, and the development of glycan array, glycosylation probes, and inhibitors of carbohydrate-associated enzymes or receptors. These novel methodologies and tools have facilitated our understanding of the significance of glycosylation and development of carbohydrate-derived medicines that bring the field to the next level of scientific and medical significance.
Topics: Carbohydrates; Glycosylation; Polysaccharides; Proteins; Translational Research, Biomedical
PubMed: 33125238
DOI: 10.1021/acs.joc.0c01834 -
Antiviral Research Dec 2020N-linked glycosylation is the most common form of protein glycosylation and is required for the proper folding, trafficking, and/or receptor binding of some host and... (Review)
Review
N-linked glycosylation is the most common form of protein glycosylation and is required for the proper folding, trafficking, and/or receptor binding of some host and viral proteins. As viruses lack their own glycosylation machinery, they are dependent on the host's machinery for these processes. Certain iminosugars are known to interfere with the N-linked glycosylation pathway by targeting and inhibiting α-glucosidases I and II in the endoplasmic reticulum (ER). Perturbing ER α-glucosidase function can prevent these enzymes from removing terminal glucose residues on N-linked glycans, interrupting the interaction between viral glycoproteins and host chaperone proteins that is necessary for proper folding of the viral protein. Iminosugars have demonstrated broad-spectrum antiviral activity in vitro and in vivo against multiple viruses. This review discusses the broad activity of iminosugars against Flaviviridae. Iminosugars have shown favorable activity against multiple members of the Flaviviridae family in vitro and in murine models of disease, although the activity and mechanism of inhibition can be virus-specfic. While iminosugars are not currently approved for the treatment of viral infections, their potential use as future host-targeted antiviral (HTAV) therapies continues to be investigated.
Topics: Animals; Antiviral Agents; Flaviviridae; Flaviviridae Infections; Glycoside Hydrolase Inhibitors; Glycosylation; Host Microbial Interactions; Humans; Imino Sugars; Mice; Viral Proteins; alpha-Glucosidases
PubMed: 32768411
DOI: 10.1016/j.antiviral.2020.104881 -
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 -
Mass Spectrometry Reviews Mar 2023Glycosylation is an important posttranslational modifier of proteins and lipid conjugates critical for the stability and function of these macromolecules. Particularly... (Review)
Review
Glycosylation is an important posttranslational modifier of proteins and lipid conjugates critical for the stability and function of these macromolecules. Particularly important are N-linked glycans attached to asparagine residues in proteins. N-glycans have well-defined roles in protein folding, cellular trafficking and signal transduction, and alterations to them are implicated in a variety of diseases. However, the non-template driven biosynthesis of these N-glycans leads to significant structural diversity, making it challenging to identify the most biologically and clinically relevant species using conventional analyses. Advances in mass spectrometry instrumentation and data acquisition, as well as in enzymatic and chemical sample preparation strategies, have positioned mass spectrometry approaches as powerful analytical tools for the characterization of glycosylation in health and disease. Imaging mass spectrometry expands upon these strategies by capturing the spatial component of a glycan's distribution in-situ, lending additional insight into the organization and function of these molecules. Herein we review the ongoing evolution of glycan imaging mass spectrometry beginning with widely adopted tissue imaging approaches and expanding to other matrices and sample types with potential research and clinical implications. Adaptations of these techniques, along with their applications to various states of disease, are discussed. Collectively, glycan imaging mass spectrometry analyses broaden our understanding of the biological and clinical relevance of N-glycosylation to human disease.
Topics: Humans; Mass Spectrometry; Glycosylation; Polysaccharides; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
PubMed: 34392557
DOI: 10.1002/mas.21725 -
Current Opinion in Structural Biology Jun 2020Post-translational modifications (PTMs) drive the diversity of the proteome and broadly regulate protein function. Interplay between different types of PTMs further... (Review)
Review
Post-translational modifications (PTMs) drive the diversity of the proteome and broadly regulate protein function. Interplay between different types of PTMs further enables tight and dynamic fine-tuning of molecular functions. O-glycosylation on serine, threonine, and tyrosine residues is a major PTM with diverse roles in development, differentiation, pathogenesis, and proteolytic processing. Other examples of cross-talk between PTMs also exists, such as PSGL-1, where the combined presence of N-terminal sulfotyrosines and O-glycans is pivotal for selectin binding. A handful of other related examples of O-glycans and sulfotyrosine co-localization has been described but it is not yet recognized as a general regulatory phenomenon. In this review, we highlight the emerging global pattern of co-localization of cell-surface and extracellular sulfotyrosines with O-glycans, which we term ‘multi-motif’ interactions, from a wide range of protein classes. We also discuss the barriers, and existing and future tools needed to dissect the biological impact and biomedical potential.
Topics: Animals; Glycomics; Glycoproteins; Glycosylation; Humans; Protein Processing, Post-Translational; Tyrosine
PubMed: 31927217
DOI: 10.1016/j.sbi.2019.12.002