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BMB Reports Nov 2021Protein glycosylation is a common post-translational modification found in all living organisms. This modification in bacterial pathogens plays a pivotal role in their... (Review)
Review
Protein glycosylation is a common post-translational modification found in all living organisms. This modification in bacterial pathogens plays a pivotal role in their infectious processes including pathogenicity, immune evasion, and host-pathogen interactions. Importantly, many key proteins of host immune systems are also glycosylated and bacterial pathogens can notably modulate glycosylation of these host proteins to facilitate pathogenesis through the induction of abnormal host protein activity and abundance. In recent years, interest in studying the regulation of host protein glycosylation caused by bacterial pathogens is increasing to fully understand bacterial pathogenesis. In this review, we focus on how bacterial pathogens regulate remodeling of host glycoproteins during infections to promote the pathogenesis. [BMB Reports 2021; 54(11): 541-544].
Topics: Animals; Bacteria; Bacterial Infections; Glycoproteins; Glycosylation; Host-Pathogen Interactions; Humans; Protein Processing, Post-Translational
PubMed: 34674797
DOI: 10.5483/BMBRep.2021.54.11.129 -
Cells Apr 2020Host-pathogen interactions are fundamental to our understanding of infectious diseases. Protein glycosylation is one kind of common post-translational modification,... (Review)
Review
Host-pathogen interactions are fundamental to our understanding of infectious diseases. Protein glycosylation is one kind of common post-translational modification, forming glycoproteins and modulating numerous important biological processes. It also occurs in host-pathogen interaction, affecting host resistance or pathogen virulence often because glycans regulate protein conformation, activity, and stability, etc. This review summarizes various roles of different glycoproteins during the interaction, which include: host glycoproteins prevent pathogens as barriers; pathogen glycoproteins promote pathogens to attack host proteins as weapons; pathogens glycosylate proteins of the host to enhance virulence; and hosts sense pathogen glycoproteins to induce resistance. In addition, this review also intends to summarize the roles of lectin (a class of protein entangled with glycoprotein) in host-pathogen interactions, including bacterial adhesins, viral lectins or host lectins. Although these studies show the importance of protein glycosylation in host-pathogen interaction, much remains to be discovered about the interaction mechanism.
Topics: Animals; Glycoproteins; Glycosylation; Host-Pathogen Interactions; Humans; Lectins; Polysaccharides; Protein Processing, Post-Translational
PubMed: 32326128
DOI: 10.3390/cells9041022 -
Current Opinion in Biotechnology Dec 2022Proteins continue to represent a large fraction of the therapeutics market, reaching over a hundred billion dollars in market size globally. One key feature of protein... (Review)
Review
Proteins continue to represent a large fraction of the therapeutics market, reaching over a hundred billion dollars in market size globally. One key feature of protein modification that can affect both structure and function is the addition of glycosylation following protein folding, leading to regulatory requirements for the accurate assessment of protein attributes, including glycan structures. The non-template-driven, innately heterogeneous N-glycosylation process thus requires accurate detection to robustly generate protein therapies. A challenge exists in the timely detection of protein glycosylation without labor-intensive manipulation. In this article, we discuss progress toward N-glycoprotein control, focusing on novel control strategies and the advancement of rapid, high-throughput analysis methods.
Topics: Glycosylation; Protein Processing, Post-Translational; Recombinant Proteins; Proteomics; Glycoproteins; Polysaccharides
PubMed: 36126382
DOI: 10.1016/j.copbio.2022.102788 -
Equine Veterinary Journal Mar 2022Carpal osteochondral fragmentation and subsequent post-traumatic osteoarthritis (PTOA) are leading causes of wastage in the equine athlete. Identification of synovial...
BACKGROUND
Carpal osteochondral fragmentation and subsequent post-traumatic osteoarthritis (PTOA) are leading causes of wastage in the equine athlete. Identification of synovial fluid biomarkers could contribute to the diagnosis and understanding of osteoarthritis (OA) pathophysiology.
OBJECTIVE
The aim of this study was to identify differentially expressed metabolic and glycosylation pathways in synovial fluid from healthy horses and horses with naturally occurring carpal OA.
STUDY DESIGN
Cross-sectional, in vivo metabolomics and glycomics study.
METHODS
In cohort 1, carpal synovial fluid (n = 12 horses; n = 6 healthy, n = 6 OA) was analysed using high-resolution liquid chromatography mass spectrometry (LC-MS). In cohort 2 (n = 40 horses; n = 20 healthy, n = 20 OA), carpal synovial fluid was analysed using lectin microarrays and a lubricin sandwich ELISA.
RESULTS
Metabolomic analysis identified >4900 LC-MS features of which 84 identifiable metabolites were differentially expressed (P < .05) between healthy and OA joints, including key pathways related to inflammation (histidine and tryptophan metabolism), oxidative stress (arginine biosynthesis) and collagen metabolism (lysine metabolism). Principle Component Analysis and Partial Least Squares Discriminant Analysis demonstrated separation between healthy and OA synovial fluid. Lectin microarrays identified distinct glycosylation patterns between healthy and OA synovial fluid, including increased Core 1/Core 3 O-glycosylation, increased α-2,3 sialylation and decreased α-1,2 fucosylation in OA. O-glycans predominated over N-glycans in all synovial fluid samples, and synovial fluid lubricin was increased in OA joints as compared to controls.
MAIN LIMITATIONS
The sample size in cohort 1 was limited, and there is inherent variation in severity and duration of joint injury in naturally occurring OA. However, LC-MS identified up to 5000 unique features.
CONCLUSIONS
These data suggest new potential diagnostic and therapeutic targets for equine OA. Future targeted metabolomic and glycomic studies should be performed to verify these results. Lectin microarrays could be investigated as a potential screening tool for the diagnosis and therapeutic monitoring of equine OA.
Topics: Animals; Biomarkers; Cross-Sectional Studies; Glycosylation; Horse Diseases; Horses; Joint Diseases; Osteoarthritis; Synovial Fluid
PubMed: 33587757
DOI: 10.1111/evj.13440 -
Analytical and Bioanalytical Chemistry Dec 2021The COVID-19 pandemic is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Similar to other coronaviruses, its particles are composed of four... (Review)
Review
The COVID-19 pandemic is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Similar to other coronaviruses, its particles are composed of four structural proteins: spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins. S, E, and M proteins are glycosylated, and the N protein is phosphorylated. The S protein is involved in the interaction with the host receptor human angiotensin-converting enzyme 2 (hACE2), which is also heavily glycosylated. Recent studies have revealed several other potential host receptors or factors that can increase or modulate the SARS-CoV-2 infection. Interestingly, most of these molecules bear carbohydrate residues. While glycans acquired by the viruses through the hijacking of the host machinery help the viruses in their infectivity, they also play roles in immune evasion or modulation. Glycans play complex roles in viral pathobiology, both on their own and in association with carrier biomolecules, such as proteins or glycosaminoglycans (GAGs). Understanding these roles in detail can help in developing suitable strategies for prevention and therapy of COVID-19. In this review, we sought to emphasize the interplay of SARS-CoV-2 glycosylated proteins and their host receptors in viral attachment, entry, replication, and infection. Moreover, the implications for future therapeutic interventions targeting these glycosylated biomolecules are also discussed in detail.
Topics: Angiotensin-Converting Enzyme 2; COVID-19; Carbohydrate Conformation; Glycosylation; Humans; Polysaccharides; Protein Conformation; SARS-CoV-2; Spike Glycoprotein, Coronavirus
PubMed: 34235568
DOI: 10.1007/s00216-021-03499-x -
Expert Review of Proteomics May 2016Glycosylation is one of the most prominent and extensively studied protein post-translational modifications. However, traditional proteomic studies at the peptide level... (Review)
Review
Glycosylation is one of the most prominent and extensively studied protein post-translational modifications. However, traditional proteomic studies at the peptide level (bottom-up) rarely characterize intact glycopeptides (glycosylated peptides without removing glycans), so no glycoprotein heterogeneity information is retained. Intact glycopeptide characterization, on the other hand, provides opportunities to simultaneously elucidate the glycan structure and the glycosylation site needed to reveal the actual biological function of protein glycosylation. Recently, significant improvements have been made in the characterization of intact glycopeptides, ranging from enrichment and separation, mass spectroscopy (MS) detection, to bioinformatics analysis. In this review, we recapitulated currently available intact glycopeptide characterization methods with respect to their advantages and limitations as well as their potential applications.
Topics: Animals; Glycomics; Glycopeptides; Glycosylation; Humans; Mass Spectrometry; Proteomics
PubMed: 27140194
DOI: 10.1586/14789450.2016.1172965 -
Hua Xi Kou Qiang Yi Xue Za Zhi = Huaxi... Jun 2018Protein glycosylation is one of the most important protein post-translational modifications that can affect life activities by endowing the protein with various... (Review)
Review
Protein glycosylation is one of the most important protein post-translational modifications that can affect life activities by endowing the protein with various structural and functional features. Saliva is an easy-to-obtain, noninvasive body fluid that contains components originating from serum, gingival crevicular fluid, and oropharyngeal mucosae. In recent years, understanding of saliva has been constantly updated with the developments in related research. Studies have shown that salivary proteins can be used as diagnostic markers for certain diseases, and changes of protein glycosylation in saliva are generally considered to be related to many diseases. In this review, salivary protein glycosylation and its relationship with systemic and oral diseases were discussed.
Topics: Gingival Crevicular Fluid; Glycosylation; Humans; Mouth Diseases; Saliva; Salivary Proteins and Peptides
PubMed: 29984939
DOI: 10.7518/hxkq.2018.03.020 -
Nano Letters Jul 2022Although nanopores can be used for single-molecule sequencing of nucleic acids using low-cost portable devices, the characterization of proteins and their modifications...
Although nanopores can be used for single-molecule sequencing of nucleic acids using low-cost portable devices, the characterization of proteins and their modifications has yet to be established. Here, we show that hydrophilic or glycosylated peptides translocate too quickly across FraC nanopores to be recognized. However, high ionic strengths (i.e., 3 M LiCl) and low pH (i.e., pH 3) together with using a nanopore with a phenylalanine at its constriction allows the recognition of hydrophilic peptides, and to distinguish between mono- and diglycosylated peptides. Using these conditions, we devise a nanopore method to detect, characterize, and quantify post-translational modifications in generic proteins, which is one of the pressing challenges in proteomic analysis.
Topics: Glycosylation; Nanopores; Nanotechnology; Peptides; Proteins; Proteomics
PubMed: 35766994
DOI: 10.1021/acs.nanolett.2c01338 -
PLoS Pathogens Nov 2019Fungal pathogenesis depends on accurate secretion and location of virulence factors which drive host colonization. Protein glycosylation is a common posttranslational...
Fungal pathogenesis depends on accurate secretion and location of virulence factors which drive host colonization. Protein glycosylation is a common posttranslational modification of cell wall components and other secreted factors, typically required for correct protein localization, secretion and function. Thus, the absence of glycosylation is associated with animal and plant pathogen avirulence. While the relevance of protein glycosylation for pathogenesis has been well established, the main glycoproteins responsible for the loss of virulence observed in glycosylation-defective fungi have not been identified. Here, we devise a proteomics approach to identify such proteins and use it to demonstrate a role for the highly conserved protein disulfide isomerase Pdi1 in virulence. We show that efficient Pdi1 N-glycosylation, which promotes folding into the correct protein conformation, is required for full pathogenic development of the corn smut fungus Ustilago maydis. Remarkably, the observed virulence defects are reminiscent of those seen in glycosylation-defective cells suggesting that the N-glycosylation of Pdi1 is necessary for the full secretion of virulence factors. All these observations, together with the fact that Pdi1 protein and RNA expression levels rise upon virulence program induction, suggest that Pdi1 glycosylation is important for normal pathogenic development in U. maydis. Our results provide new insights into the role of glycosylation in fungal pathogenesis.
Topics: Glycoproteins; Glycosylation; Plant Diseases; Protein Disulfide-Isomerases; Proteome; Ustilago; Virulence; Virulence Factors; Zea mays
PubMed: 31730668
DOI: 10.1371/journal.ppat.1007687 -
Glycobiology Dec 2023N-linked protein glycosylation is a post-translational modification that exists in all domains of life. It involves two consecutive steps: (i) biosynthesis of a... (Review)
Review
N-linked protein glycosylation is a post-translational modification that exists in all domains of life. It involves two consecutive steps: (i) biosynthesis of a lipid-linked oligosaccharide (LLO), and (ii) glycan transfer from the LLO to asparagine residues in secretory proteins, which is catalyzed by the integral membrane enzyme oligosaccharyltransferase (OST). In the last decade, structural and functional studies of the N-glycosylation machinery have increased our mechanistic understanding of the pathway. The structures of bacterial and eukaryotic glycosyltransferases involved in LLO elongation provided an insight into the mechanism of LLO biosynthesis, whereas structures of OST enzymes revealed the molecular basis of sequon recognition and catalysis. In this review, we will discuss approaches used and insight obtained from these studies with a special emphasis on the design and preparation of substrate analogs.
Topics: Glycosylation; Hexosyltransferases; Lipopolysaccharides; Polysaccharides; Glycosyltransferases
PubMed: 37399117
DOI: 10.1093/glycob/cwad053