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Autoimmunity Reviews Sep 2023Psoriatic arthritis (PsA) is an inflammatory complex condition. Posttranslational modifications influence almost all aspects of normal cell biology and pathogenesis. The... (Review)
Review
BACKGROUND AND AIMS
Psoriatic arthritis (PsA) is an inflammatory complex condition. Posttranslational modifications influence almost all aspects of normal cell biology and pathogenesis. The aim of this systematic review was to collect all published evidence regarding posttranslational modifications in PsA, and the main outcome was to evaluate an association between disease outcomes and specific posttranslational modifications in PsA.
METHODS
A systematic electronic search was performed in Medline, PubMed, Cochrane, Virtual Health Library, and Embase databases. A total of 587 articles were identified; 59 were evaluated after removing duplicates and scanning, of which 47 were included. A descriptive analysis was conducted, with results grouped according to the type of posttranslational modification evaluated. The protocol was registered at the PROSPERO database.
RESULTS
Seven posttranslational modifications were identified: citrullination, carbamylation, phosphorylation, glycosylation, acetylation, methylation, and oxidative stress. Anti-citrullinated peptide and anti-carbamylated protein have been evaluated in rheumatoid arthritis. There is now information suggesting that these antibodies may be helpful in improving the diagnosis of PsA and that they may demonstrate a correlation with worse disease progression (erosions, polyarticular involvement, and poor treatment response). Glycosylation was associated with increased inflammation and phosphorylation products related to the expression of SIRT2 and pSTAT3 or the presence of Th17 and cytokine interleukin-22, suggesting a possible therapeutic target.
CONCLUSIONS
Posttranslational modifications often play a key role in modulating protein function in PsA and correlate with disease outcomes. Citrullination, carbamylation, phosphorylation, glycosylation, acetylation, methylation, and oxidative stress were identified as associated with diagnosis and prognosis.
Topics: Humans; Arthritis, Psoriatic; Protein Processing, Post-Translational; Citrullination; Glycosylation; Arthritis, Rheumatoid
PubMed: 37487969
DOI: 10.1016/j.autrev.2023.103393 -
Frontiers in Immunology 2023Protein glycosylation is a widespread posttranslational modification that can impact the function of proteins. Dysregulated protein glycosylation has been linked to... (Review)
Review
Protein glycosylation is a widespread posttranslational modification that can impact the function of proteins. Dysregulated protein glycosylation has been linked to several diseases, including chronic respiratory diseases (CRDs). CRDs pose a significant public health threat globally, affecting the airways and other lung structures. Emerging researches suggest that glycosylation plays a significant role in regulating inflammation associated with CRDs. This review offers an overview of the abnormal glycoenzyme activity and corresponding glycosylation changes involved in various CRDs, including chronic obstructive pulmonary disease, asthma, cystic fibrosis, idiopathic pulmonary fibrosis, pulmonary arterial hypertension, non-cystic fibrosis bronchiectasis, and lung cancer. Additionally, this review summarizes recent advances in glycomics and glycoproteomics-based protein glycosylation analysis of CRDs. The potential of glycoenzymes and glycoproteins for clinical use in the diagnosis and treatment of CRDs is also discussed.
Topics: Humans; Glycosylation; Respiration Disorders; Glycoproteins; Lung; Inflammation
PubMed: 37256139
DOI: 10.3389/fimmu.2023.1168023 -
Arthritis Research & Therapy Jun 2023Osteoarthritis (OA) is the most common form of arthritis, affecting millions of aging people. Investigation of abnormal glycosylation is essential for the understanding...
BACKGROUND
Osteoarthritis (OA) is the most common form of arthritis, affecting millions of aging people. Investigation of abnormal glycosylation is essential for the understanding of pathological mechanisms of OA.
METHODS
The total protein was isolated from OA (n = 13) and control (n = 11) cartilages. Subsequently, glycosylation alterations of glycoproteins in OA cartilage were investigated by lectin microarrays and intact glycopeptides analysis. Finally, the expression of glycosyltransferases involved in the synthesis of altered glycosylation was assessed by qPCR and GEO database.
RESULTS
Our findings revealed that several glycopatterns, such as α-1,3/6 fucosylation and high-mannose type of N-glycans were altered in OA cartilages. Notably, over 27% of identified glycopeptides (109 glycopeptides derived from 47 glycoproteins mainly located in the extracellular region) disappeared or decreased in OA cartilages, which is related to the cartilage matrix degradation. Interestingly, the microheterogeneity of N-glycans on fibronectin and aggrecan core protein was observed in OA cartilage. Our results combined with GEO data indicated that the pro-inflammatory cytokines altered the expression of glycosyltransferases (ALG3, ALG5, MGAT4C, and MGAT5) which may contribute to the alterations in glycosylation.
CONCLUSION
Our study revealed the abnormal glycopatterns and heterogeneities of site-specific glycosylation associated with OA. To our knowledge, it is the first time that the heterogeneity of site-specific N-glycans was reported in OA cartilage. The results of gene expression analysis suggested that the expression of glycosyltransferases was impacted by pro-inflammatory cytokines, which may facilitate the degradation of protein and accelerate the process of OA. Our findings provide valuable information for the understanding of molecular mechanisms in the pathogenesis of OA.
Topics: Humans; Osteoarthritis; Glycosylation; Glycomics; Glycoproteins; Cartilage; Cytokines
PubMed: 37308935
DOI: 10.1186/s13075-023-03084-w -
Proteomics Aug 2022Glycosylation of viral proteins is required for the progeny formation and infectivity of virtually all viruses. It is increasingly clear that distinct glycans also play... (Review)
Review
Glycosylation of viral proteins is required for the progeny formation and infectivity of virtually all viruses. It is increasingly clear that distinct glycans also play pivotal roles in the virus's ability to shield and evade the host's immune system. Recently, there has been a great advancement in structural identification and quantitation of viral glycosylation, especially spike proteins. Given the ongoing pandemic and the high demand for structure analysis of SARS-CoV-2 densely glycosylated spike protein, mass spectrometry methodologies have been employed to accurately determine glycosylation patterns. There are still many challenges in the determination of site-specific glycosylation of SARS-CoV-2 viral spike protein. This is compounded by some conflicting results regarding glycan site occupancy and glycan structural characterization. These are probably due to differences in the expression systems, form of expressed spike glycoprotein, MS methodologies, and analysis software. In this review, we recap the glycosylation of spike protein and compare among various studies. Also, we describe the most recent advancements in glycosylation analysis in greater detail and we explain some misinterpretation of previously observed data in recent publications. Our study provides a comprehensive view of the spike protein glycosylation and highlights the importance of consistent glycosylation determination.
Topics: COVID-19; Glycosylation; Humans; Mass Spectrometry; Polysaccharides; SARS-CoV-2; Spike Glycoprotein, Coronavirus
PubMed: 35700310
DOI: 10.1002/pmic.202100322 -
Cells Aug 2020The protein glycosylation is a post-translational modification of crucial importance for its involvement in molecular recognition, protein trafficking, regulation, and... (Review)
Review
The protein glycosylation is a post-translational modification of crucial importance for its involvement in molecular recognition, protein trafficking, regulation, and inflammation. Indeed, abnormalities in protein glycosylation are correlated with several disease states such as cancer, inflammatory diseases, and congenial disorders. The understanding of cellular mechanisms through the elucidation of glycan composition encourages researchers to find analytical solutions for their detection. Actually, the multiplicity and diversity of glycan structures bond to the proteins, the variations in polarity of the individual saccharide residues, and the poor ionization efficiencies make their detection much trickier than other kinds of biopolymers. An overview of the most prominent techniques based on mass spectrometry (MS) for protein glycosylation (glycoproteomics) studies is here presented. The tricks and pre-treatments of samples are discussed as a crucial step prodromal to the MS analysis to improve the glycan ionization efficiency. Therefore, the different instrumental MS mode is also explored for the qualitative and quantitative analysis of glycopeptides and the glycans structural composition, thus contributing to the elucidation of biological mechanisms.
Topics: Glycosylation; Humans; Mass Spectrometry; Protein Processing, Post-Translational; Proteomics
PubMed: 32872358
DOI: 10.3390/cells9091986 -
Molecular & Cellular Proteomics : MCP 2021Mass spectrometry-based glycoproteomics has gone through some incredible developments over the last few years. Technological advances in glycopeptide enrichment,... (Review)
Review
Mass spectrometry-based glycoproteomics has gone through some incredible developments over the last few years. Technological advances in glycopeptide enrichment, fragmentation methods, and data analysis workflows have enabled the transition of glycoproteomics from a niche application, mainly focused on the characterization of isolated glycoproteins, to a mature technology capable of profiling thousands of intact glycopeptides at once. In addition to numerous biological discoveries catalyzed by the technology, we are also observing an increase in studies focusing on global protein glycosylation and the relationship between multiple glycosylation sites on the same protein. It has become apparent that just describing protein glycosylation in terms of micro- and macro-heterogeneity, respectively, the variation and occupancy of glycans at a given site, is not sufficient to describe the observed interactions between sites. In this perspective we propose a new term, meta-heterogeneity, to describe a higher level of glycan regulation: the variation in glycosylation across multiple sites of a given protein. We provide literature examples of extensive meta-heterogeneity on relevant proteins such as antibodies, erythropoietin, myeloperoxidase, and a number of serum and plasma proteins. Furthermore, we postulate on the possible biological reasons and causes behind the intriguing meta-heterogeneity observed in glycoproteins.
Topics: Animals; Glycoproteins; Glycosylation; Humans; Software
PubMed: 33561609
DOI: 10.1074/mcp.R120.002093 -
International Journal of Molecular... Dec 2022Glycosylation, which consists of the enzymatic addition of sugars to proteins and lipids, is one of the most important post-co-synthetic modifications of these... (Review)
Review
Glycosylation, which consists of the enzymatic addition of sugars to proteins and lipids, is one of the most important post-co-synthetic modifications of these molecules, profoundly affecting their activity. Although the presence of carbohydrate chains is crucial for fine-tuning the interactions between cells and molecules, glycosylation is an intrinsically stochastic process regulated by the relative abundance of biosynthetic (glycosyltransferases) and catabolic (glycosidases) enzymes, as well as sugar carriers and other molecules. Non-coding RNAs, which include microRNAs, long non-coding RNAs and circRNAs, establish a complex network of reciprocally interacting molecules whose final goal is the regulation of mRNA expression. Likewise, these interactions are stochastically regulated by ncRNA abundance. Thus, while protein sequence is deterministically dictated by the DNA/RNA/protein axis, protein abundance and activity are regulated by two stochastic processes acting, respectively, before and after the biosynthesis of the protein axis. Consequently, the worlds of glycosylation and ncRNA are closely interconnected and mutually interacting. In this paper, we will extensively review the many faces of the ncRNA-glycosylation interplay in cancer and other physio-pathological conditions.
Topics: Humans; Glycosylation; Glycosyltransferases; MicroRNAs; Carbohydrates; Neoplasms; RNA, Long Noncoding
PubMed: 36555445
DOI: 10.3390/ijms232415804 -
Molecular Biology Reports Aug 2022N-linked protein glycosylation is an essential co-and posttranslational protein modification that occurs in all three domains of life; the assembly of N-glycans follows... (Review)
Review
N-linked protein glycosylation is an essential co-and posttranslational protein modification that occurs in all three domains of life; the assembly of N-glycans follows a complex sequence of events spanning the (Endoplasmic Reticulum) ER and the Golgi apparatus. It has a significant impact on both physicochemical properties and biological functions. It plays a significant role in protein folding and quality control, glycoprotein interaction, signal transduction, viral attachment, and immune response to infection. Glycoengineering of protein employed for improving protein properties and plays a vital role in the production of recombinant glycoproteins and struggles to humanize recombinant therapeutic proteins. It considers an alternative platform for biopharmaceuticals production. Many immune proteins and antibodies are glycosylated. Pathogen's glycoproteins play vital roles during the infection cycle and their expression of specific oligosaccharides via the N-glycosylation pathway to evade detection by the host immune system. This review focuses on the aspects of N-glycosylation processing, glycoengineering approaches, their role in viral attachment, and immune responses to infection.
Topics: Endoplasmic Reticulum; Glycoproteins; Glycosylation; Golgi Apparatus; Humans; Polysaccharides; Recombinant Proteins; Virus Diseases
PubMed: 35364718
DOI: 10.1007/s11033-022-07359-4 -
Current Opinion in Structural Biology Jun 2021
Topics: Databases, Protein; Glycoproteins; Glycosylation
PubMed: 33879390
DOI: 10.1016/j.sbi.2021.03.002 -
International Journal of Molecular... Mar 2022-Glycosylation (NG) and disulfide bonds (DBs) are two prevalent co/post-translational modifications (PTMs) that are often conserved and coexist in membrane and secreted... (Review)
Review
-Glycosylation (NG) and disulfide bonds (DBs) are two prevalent co/post-translational modifications (PTMs) that are often conserved and coexist in membrane and secreted proteins involved in a large number of diseases. Both in the past and in recent times, the enzymes and chaperones regulating these PTMs have been constantly discovered to directly interact with each other or colocalize in the ER. However, beyond a few model proteins, how such cooperation affects -glycan modification and disulfide bonding at selective sites in individual proteins is largely unknown. Here, we reviewed the literature to discover the current status in understanding the relationships between NG and DBs in individual proteins. Our results showed that more than 2700 human proteins carry both PTMs, and fewer than 2% of them have been investigated in the associations between NG and DBs. We summarized both these proteins with the reported relationships in the two PTMs and the tools used to discover the relationships. We hope that, by exposing this largely understudied field, more investigations can be encouraged to unveil the hidden relationships of NG and DBs in the majority of membranes and secreted proteins for pathophysiological understanding and biotherapeutic development.
Topics: Disulfides; Glycosylation; Humans; Molecular Chaperones; Protein Domains; Protein Processing, Post-Translational
PubMed: 35409101
DOI: 10.3390/ijms23073742