-
Cardiovascular Research Mar 2021Protein glycosylation is a post-translational modification consisting in the enzymatic attachment of carbohydrate chains to specific residues of the protein sequence.... (Review)
Review
Protein glycosylation is a post-translational modification consisting in the enzymatic attachment of carbohydrate chains to specific residues of the protein sequence. Several types of glycosylation have been described, with N-glycosylation and O-glycosylation being the most common types impacting on crucial biological processes, such as protein synthesis, trafficking, localization, and function. Genetic defects in genes involved in protein glycosylation may result in altered production and activity of several proteins, with a broad range of clinical manifestations, including dyslipidaemia and atherosclerosis. A large number of apolipoproteins, lipoprotein receptors, and other proteins involved in lipoprotein metabolism are glycosylated, and alterations in their glycosylation profile are associated with changes in their expression and/or function. Rare genetic diseases and population genetics have provided additional information linking protein glycosylation to the regulation of lipoprotein metabolism.
Topics: Animals; Apolipoproteins; Atherosclerosis; Dyslipidemias; Genetic Predisposition to Disease; Glycosylation; Humans; Lipid Metabolism; Lipoproteins; Phenotype; Plaque, Atherosclerotic; Protein Processing, Post-Translational; Receptors, Lipoprotein
PubMed: 32886765
DOI: 10.1093/cvr/cvaa252 -
Biomolecules Sep 2022This article is part of the Special Issue Glycosylation-The Most Diverse Post-Translational Modification [...].
This article is part of the Special Issue Glycosylation-The Most Diverse Post-Translational Modification [...].
Topics: Glycosylation; Protein Processing, Post-Translational
PubMed: 36139152
DOI: 10.3390/biom12091313 -
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 -
ELife Mar 2023Cancer secretome is a reservoir for aberrant glycosylation. How therapies alter this post- translational cancer hallmark and the consequences thereof remain elusive....
Cancer secretome is a reservoir for aberrant glycosylation. How therapies alter this post- translational cancer hallmark and the consequences thereof remain elusive. Here, we show that an elevated secretome fucosylation is a pan-cancer signature of both response and resistance to multiple targeted therapies. Large-scale pharmacogenomics revealed that fucosylation genes display widespread association with resistance to these therapies. In cancer cell cultures, xenograft mouse models, and patients, targeted kinase inhibitors distinctively induced core fucosylation of secreted proteins less than 60 kDa. Label-free proteomics of N-glycoproteomes identified fucosylation of the antioxidant PON1 as a critical component of the therapy-induced secretome (TIS). N-glycosylation of TIS and target core fucosylation of PON1 are mediated by the fucose salvage-FUT8-SLC35C1 axis with PON3 directly modulating GDP-Fuc transfer on PON1 scaffolds. Core fucosylation in the Golgi impacts PON1 stability and folding prior to secretion, promoting a more degradation-resistant PON1. Global and PON1-specific secretome de-N-glycosylation both limited the expansion of resistant clones in a tumor regression model. We defined the resistance-associated transcription factors (TFs) and genes modulated by the N-glycosylated TIS via a focused and transcriptome-wide analyses. These genes characterize the oxidative stress, inflammatory niche, and unfolded protein response as important factors for this modulation. Our findings demonstrate that core fucosylation is a common modification indirectly induced by targeted therapies that paradoxically promotes resistance.
Topics: Humans; Animals; Mice; Glycosylation; Secretome; Protein Processing, Post-Translational; Aryldialkylphosphatase
PubMed: 36961502
DOI: 10.7554/eLife.75191 -
Frontiers in Endocrinology 2023Osteoarthritis (OA) is the most common degenerative and progressive joint disease. Cellular senescence is an irreversible cell cycle arrest progressive with age, while...
Osteoarthritis (OA) is the most common degenerative and progressive joint disease. Cellular senescence is an irreversible cell cycle arrest progressive with age, while protein glycosylation is the most abundant post-translational modification, regulating various cellular and biological pathways. The implication of either chondrocyte senescence or protein glycosylation in the OA pathogenesis has been extensively and individually studied. In this study, we aimed to investigate the possible relationship between chondrocyte senescence and protein glycosylation on the pathogenesis of OA using single-cell RNA sequencing datasets of clinical OA specimens deposited in the Gene Expression Omnibus database with a different cohort. We demonstrated that both cellular senescence signal and protein glycosylation pathways in chondrocytes are validly associated with OA pathogenesis. In addition, the cellular senescence signal is well-connected to the O-linked glycosylation pathway in OA chondrocyte and vice-versa. The expression levels of the polypeptide N-acetylgalactosaminyltransferase (GALNT) family, which is essential for the biosynthesis of O-Glycans at the early stage, are highly upregulated in OA chondrocytes. Moreover, the expression levels of the GALNT family are prominently associated with chondrocyte senescence as well as pathological features of OA. Collectively, these findings uncover a crucial relationship between chondrocyte senescence and O-linked glycosylation on the OA pathophysiology, thereby revealing a potential target for OA.
Topics: Humans; Chondrocytes; Glycosylation; Osteoarthritis; Cellular Senescence; Protein Processing, Post-Translational
PubMed: 37265706
DOI: 10.3389/fendo.2023.1153689 -
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 -
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 -
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