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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 -
Biomolecules Feb 2024Glycosylation, a prevalent post-translational modification, plays a pivotal role in regulating intricate cellular processes by covalently attaching glycans to... (Review)
Review
Glycosylation, a prevalent post-translational modification, plays a pivotal role in regulating intricate cellular processes by covalently attaching glycans to macromolecules. Dysregulated glycosylation is linked to a spectrum of diseases, encompassing cancer, neurodegenerative disorders, congenital disorders, infections, and inflammation. This review delves into the intricate interplay between glycosylation and protein conformation, with a specific focus on the profound impact of N-glycans on the selection of distinct protein conformations characterized by distinct interactomes-namely, protein assemblies-under normal and pathological conditions across various diseases. We begin by examining the spike protein of the SARS virus, illustrating how N-glycans regulate the infectivity of pathogenic agents. Subsequently, we utilize the prion protein and the chaperone glucose-regulated protein 94 as examples, exploring instances where N-glycosylation transforms physiological protein structures into disease-associated forms. Unraveling these connections provides valuable insights into potential therapeutic avenues and a deeper comprehension of the molecular intricacies that underlie disease conditions. This exploration of glycosylation's influence on protein conformation effectively bridges the gap between the glycome and disease, offering a comprehensive perspective on the therapeutic implications of targeting conformational mutants and their pathologic assemblies in various diseases. The goal is to unravel the nuances of these post-translational modifications, shedding light on how they contribute to the intricate interplay between protein conformation, assembly, and disease.
Topics: Glycosylation; Protein Processing, Post-Translational; Polysaccharides; Protein Conformation; Prions
PubMed: 38540703
DOI: 10.3390/biom14030282 -
Nature Communications Jun 2023Recent interest in targeted therapies has been sparked by the study of MHC-associated peptides (MAPs) that undergo post-translational modifications (PTMs), particularly...
Recent interest in targeted therapies has been sparked by the study of MHC-associated peptides (MAPs) that undergo post-translational modifications (PTMs), particularly glycosylation. In this study, we introduce a fast computational workflow that merges the MSFragger-Glyco search algorithm with a false discovery rate control for glycopeptide analysis from mass spectrometry-based immunopeptidome data. By analyzing eight large-scale publicly available studies, we find that glycosylated MAPs are predominantly presented by MHC class II. Here, we present HLA-Glyco, a comprehensive resource containing over 3,400 human leukocyte antigen (HLA) class II N-glycopeptides from 1,049 distinct protein glycosylation sites. This resource provides valuable insights, including high levels of truncated glycans, conserved HLA-binding cores, and differences in glycosylation positional specificity between HLA allele groups. We integrate the workflow within the FragPipe computational platform and provide HLA-Glyco as a free web resource. Overall, our work provides a valuable tool and resource to aid the nascent field of glyco-immunopeptidomics.
Topics: Humans; Glycosylation; Protein Processing, Post-Translational; Algorithms; Genes, MHC Class II; Glycopeptides
PubMed: 37308510
DOI: 10.1038/s41467-023-39270-2 -
Mass Spectrometry Reviews Aug 2019Protein glycosylation is ubiquitous in biological systems and plays essential roles in many cellular events. Global and site-specific analysis of glycoproteins in... (Review)
Review
Protein glycosylation is ubiquitous in biological systems and plays essential roles in many cellular events. Global and site-specific analysis of glycoproteins in complex biological samples can advance our understanding of glycoprotein functions and cellular activities. However, it is extraordinarily challenging because of the low abundance of many glycoproteins and the heterogeneity of glycan structures. The emergence of mass spectrometry (MS)-based proteomics has provided us an excellent opportunity to comprehensively study proteins and their modifications, including glycosylation. In this review, we first summarize major methods for glycopeptide/glycoprotein enrichment, followed by the chemical and enzymatic methods to generate a mass tag for glycosylation site identification. We next discuss the systematic and quantitative analysis of glycoprotein dynamics. Reversible protein glycosylation is dynamic, and systematic study of glycoprotein dynamics helps us gain insight into glycoprotein functions. The last part of this review focuses on the applications of MS-based proteomics to study glycoproteins in different biological systems, including yeasts, plants, mice, human cells, and clinical samples. Intact glycopeptide analysis is also included in this section. Because of the importance of glycoproteins in complex biological systems, the field of glycoproteomics will continue to grow in the next decade. Innovative and effective MS-based methods will exponentially advance glycoscience, and enable us to identify glycoproteins as effective biomarkers for disease detection and drug targets for disease treatment. © 2019 Wiley Periodicals, Inc. Mass Spec Rev 9999: XX-XX, 2019.
Topics: Animals; Glycomics; Glycopeptides; Glycoproteins; Glycosylation; Humans; Mass Spectrometry; Polysaccharides; Proteomics
PubMed: 30605224
DOI: 10.1002/mas.21586 -
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 -
The Journal of Biological Chemistry Mar 2013Protein glycosylation is widespread throughout all three domains of life. Bacterial protein N-glycosylation and its application to engineering recombinant glycoproteins... (Review)
Review
Protein glycosylation is widespread throughout all three domains of life. Bacterial protein N-glycosylation and its application to engineering recombinant glycoproteins continue to be actively studied. Here, we focus on advances made in the last 2 years, including the characterization of novel bacterial N-glycosylation pathways, examination of pathway enzymes and evolution, biological roles of protein modification in the native host, and exploitation of the N-glycosylation pathways to create novel vaccines and diagnostics.
Topics: Animals; Bacterial Infections; Bacterial Proteins; Glycoproteins; Glycosylation; Humans; Models, Immunological; Mutation; Periplasm; Signal Transduction
PubMed: 23329827
DOI: 10.1074/jbc.R112.417857 -
Gut Microbes 2020Serine-rich repeat proteins (SRRPs) have emerged as an important group of cell surface adhesins found in a growing number of Gram-positive bacteria. Studies focused on... (Review)
Review
Serine-rich repeat proteins (SRRPs) have emerged as an important group of cell surface adhesins found in a growing number of Gram-positive bacteria. Studies focused on SRRPs from streptococci and staphylococci demonstrated that these proteins are -glycosylated on serine or threonine residues and exported via an accessory secretion (aSec) system. In pathogens, these adhesins contribute to disease pathogenesis and represent therapeutic targets. Recently, the non-canonical aSec system has been identified in the genomes of gut microbes and characterization of their associated SRRPs is beginning to unfold, showing their role in mediating attachment and biofilm formation. Here we provide an update of the occurrence, structure, and function of SRRPs across bacteria, with emphasis on the molecular and biochemical properties of SRRPs from gut symbionts, particularly Lactobacilli. These emerging studies underscore the range of ligands recognized by these adhesins and the importance of SRRP glycosylation in the interaction of gut microbes with the host.
Topics: Adhesins, Bacterial; Bacterial Proteins; Biofilms; Gastrointestinal Microbiome; Glycosylation; Gram-Positive Bacteria; Humans; Intestines; Lactobacillus; Membrane Proteins; Symbiosis
PubMed: 31035824
DOI: 10.1080/19490976.2019.1602428 -
ACS Synthetic Biology Jul 2020Protein glycosylation, the attachment of sugars to amino acid side chains, can endow proteins with a wide variety of properties of great interest to the engineering... (Review)
Review
Protein glycosylation, the attachment of sugars to amino acid side chains, can endow proteins with a wide variety of properties of great interest to the engineering biology community. However, natural glycosylation systems are limited in the diversity of glycoproteins they can synthesize, the scale at which they can be harnessed for biotechnology, and the homogeneity of glycoprotein structures they can produce. Here we provide an overview of the emerging field of synthetic glycobiology, the application of synthetic biology tools and design principles to better understand and engineer glycosylation. Specifically, we focus on how the biosynthetic and analytical tools of synthetic biology have been used to redesign glycosylation systems to obtain defined glycosylation structures on proteins for diverse applications in medicine, materials, and diagnostics. We review the key biological parts available to synthetic biologists interested in engineering glycoproteins to solve compelling problems in glycoscience, describe recent efforts to construct synthetic glycoprotein synthesis systems, and outline exemplary applications as well as new opportunities in this emerging space.
Topics: Animals; Bacteria; Biotechnology; Fungi; Glycosylation; Glycosyltransferases; Plants; Proteins; Synthetic Biology
PubMed: 32526139
DOI: 10.1021/acssynbio.0c00210 -
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 -
Future Microbiology Jan 2017Through advances in analytical methods to detect glycoproteins and to determine glycan structures, there have been increasing reports of protein glycosylation in... (Review)
Review
Through advances in analytical methods to detect glycoproteins and to determine glycan structures, there have been increasing reports of protein glycosylation in bacteria. In this review, we summarize the known pathways for bacterial protein glycosylation: lipid carrier-mediated 'en bloc' glycosylation; and cytoplasmic stepwise protein glycosylation. The exploitation of bacterial protein glycosylation systems, especially the 'mix and match' of three independent but similar pathways (oligosaccharyltransferase-mediated protein glycosylation, lipopolysaccharide and peptidoglycan biosynthesis) in Gram-negative bacteria for glycoengineering recombinant glycoproteins is also discussed.
Topics: Bacterial Proteins; Campylobacter jejuni; Glycosylation; Gram-Positive Bacteria; Helicobacter pylori; Hexosyltransferases; Lipopolysaccharides; Membrane Proteins; Neisseria gonorrhoeae; Neisseria meningitidis; Peptidoglycan; Polysaccharides; Protein Engineering; Recombinant Proteins
PubMed: 27689684
DOI: 10.2217/fmb-2016-0166