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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 -
Pharmacological Research May 2023Acute ischemic stroke (AIS) is a serious and life-threatening disease worldwide. Despite thrombolysis or endovascular thrombectomy, a sizeable fraction of patients with... (Review)
Review
Acute ischemic stroke (AIS) is a serious and life-threatening disease worldwide. Despite thrombolysis or endovascular thrombectomy, a sizeable fraction of patients with AIS have adverse clinical outcomes. In addition, existing secondary prevention strategies with antiplatelet and anticoagulant drugs therapy are not able to adequately decrease the risk of ischemic stroke recurrence. Thus, exploring novel mechanisms for doing so represents an urgent need for the prevention and treatment of AIS. Recent studies have discovered that protein glycosylation plays a critical role in the occurrence and outcome of AIS. As a common co- and post-translational modification, protein glycosylation participates in a wide variety of physiological and pathological processes by regulating the activity and function of proteins or enzymes. Protein glycosylation is involved in two causes of cerebral emboli in ischemic stroke: atherosclerosis and atrial fibrillation. Following ischemic stroke, the level of brain protein glycosylation becomes dynamically regulated, which significantly affects stroke outcome through influencing inflammatory response, excitotoxicity, neuronal apoptosis, and blood-brain barrier disruption. Drugs targeting glycosylation in the occurrence and progression of stroke may represent a novel therapeutic idea. In this review, we focus on possible perspectives about how glycosylation affects the occurrence and outcome of AIS. We then propose the potential of glycosylation as a therapeutic drug target and prognostic marker for AIS patients in the future.
Topics: Humans; Brain Ischemia; Glycosylation; Ischemic Stroke; Stroke; Treatment Outcome
PubMed: 36907285
DOI: 10.1016/j.phrs.2023.106726 -
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 -
Frontiers in Immunology 2023Post-translational modification (PTM) refers to the covalent attachment of functional groups to protein substrates, resulting in structural and functional changes. PTMs... (Review)
Review
Post-translational modification (PTM) refers to the covalent attachment of functional groups to protein substrates, resulting in structural and functional changes. PTMs not only regulate the development and progression of liver cancer, but also play a crucial role in the immune response against cancer. Cancer immunity encompasses the combined efforts of innate and adaptive immune surveillance against tumor antigens, tumor cells, and tumorigenic microenvironments. Increasing evidence suggests that immunotherapies, which harness the immune system's potential to combat cancer, can effectively improve cancer patient prognosis and prolong the survival. This review presents a comprehensive summary of the current understanding of key PTMs such as phosphorylation, ubiquitination, SUMOylation, and glycosylation in the context of immune cancer surveillance against liver cancer. Additionally, it highlights potential targets associated with these modifications to enhance the response to immunotherapies in the treatment of liver cancer.
Topics: Humans; Liver Neoplasms; Protein Processing, Post-Translational; Glycosylation; Phosphorylation; Immunologic Surveillance; Tumor Microenvironment
PubMed: 37609076
DOI: 10.3389/fimmu.2023.1230465 -
Current Opinion in Structural Biology Jun 2022Biosynthetic enzymes in the secretory pathway create distributions of glycans at each glycosite that elaborate the biophysical properties and biological functions of... (Review)
Review
Biosynthetic enzymes in the secretory pathway create distributions of glycans at each glycosite that elaborate the biophysical properties and biological functions of glycoproteins. Because the biosynthetic glycosylation reactions do not go to completion, each protein glycosite is heterogeneous with respect to glycosylation. This heterogeneity means that it is not sufficient to measure protein abundance in omics experiments. Rather, it is necessary to sample the distribution of glycosylation at each glycosite to quantify the changes that occur during biological processes. On the one hand, the use of data-dependent acquisition methods to sample glycopeptides is limited by the instrument duty cycle and the missing value problem. On the other, stepped window data-independent acquisition samples all precursors, but ion abundances are limited by duty cycle. Therefore, the ability to quantify accurately the flux in glycoprotein glycosylation that occurs during biological processes requires the exploitation of emerging mass spectrometry technologies capable of deep, comprehensive sampling and selective high confidence assignment of the complex glycopeptide mixtures. This review summarizes recent technical advances and mass spectral glycoproteomics analysis strategies and how these developments impact our ability to quantify the changes in glycosylation that occur during biological processes. We highlight specific improvements to glycopeptide characterization through activated electron dissociation, ion mobility trends and instrumentation, and efficient algorithmic approaches for glycopeptide assignment. We also discuss the emerging need for unified standards to enable interlaboratory collaborations and effective monitoring of structural changes in glycoproteins.
Topics: Glycopeptides; Glycoproteins; Glycosylation; Mass Spectrometry; Polysaccharides
PubMed: 35452871
DOI: 10.1016/j.sbi.2022.102371 -
PLoS Pathogens Oct 2023In the case of the Japanese encephalitis virus (JEV), the envelope protein (E), a major component of viral particles, contains a highly conserved N-linked glycosylation...
In the case of the Japanese encephalitis virus (JEV), the envelope protein (E), a major component of viral particles, contains a highly conserved N-linked glycosylation site (E: N154). Glycosylation of the E protein is thought to play an important role in the ability of the virus to attach to target cells during transmission; however, its role in viral particle formation and release remains poorly understood. In this study, we investigated the role of N-glycosylation of flaviviral structural proteins in viral particle formation and secretion by introducing mutations in viral structural proteins or cellular factors involved in glycoprotein transport and processing. The number of secreted subviral particles (SVPs) was significantly reduced in N154A, a glycosylation-null mutant, but increased in D67N, a mutant containing additional glycosylation sites, indicating that the amount of E glycosylation regulates the release of SVPs. SVP secretion was reduced in cells deficient in galactose, sialic acid, and N-acetylglucosamine modifications in the Golgi apparatus; however, these reductions were not significant, suggesting that glycosylation mainly plays a role in pre-Golgi transport. Fluorescent labeling of SVPs using a split green fluorescent protein (GFP) system and time-lapse imaging by retention using selective hooks (RUSH) system revealed that the glycosylation-deficient mutant was arrested before endoplasmic reticulum (ER)- Golgi transport. However, the absence of ERGIC-53 and ERGIC-L, ER-Golgi transport cargo receptors that recognize sugar chains on cargo proteins, does not impair SVP secretion. In contrast, the solubility of the N154A mutant of E or the N15A/T17A mutant of prM in cells was markedly lower than that of the wild type, and proteasome-mediated rapid degradation of these mutants was observed, indicating the significance of glycosylation of both prM and E in proper protein folding and assembly of viral particles in the ER.
Topics: Glycosylation; Flavivirus; Viral Envelope Proteins; Encephalitis Virus, Japanese; Virion
PubMed: 37819933
DOI: 10.1371/journal.ppat.1011681 -
Cells Nov 2022Glycosylation is a common post-translational modification process of proteins. Mucin-type O-glycosylation is an O-glycosylation that starts from protein serine/threonine... (Review)
Review
Glycosylation is a common post-translational modification process of proteins. Mucin-type O-glycosylation is an O-glycosylation that starts from protein serine/threonine residues. Normally, it is involved in the normal development and differentiation of cells and tissues, abnormal glycosylation can lead to a variety of diseases, especially cancer. This paper reviews the normal biosynthesis of mucin-type O-glycans and their role in the maintenance of body health, followed by the mechanisms of abnormal mucin-type O-glycosylation in the development of diseases, especially tumors, including the effects of Tn, STn, T antigen, and different glycosyltransferases, with special emphasis on their role in the development of gastric cancer. Finally, tumor immunotherapy targeting mucin-type O-glycans was discussed.
Topics: Humans; Mucins; Polysaccharides; Glycosylation; Neoplasms; Glycosyltransferases; Proteins
PubMed: 36429094
DOI: 10.3390/cells11223666 -
Orphanet Journal of Rare Diseases Aug 2023Congenital disorders of glycosylation are a group of more than 160 rare genetic defects in protein and lipid glycosylation. Since the first clinical report in 1980 of... (Review)
Review
Congenital disorders of glycosylation are a group of more than 160 rare genetic defects in protein and lipid glycosylation. Since the first clinical report in 1980 of PMM2-CDG, the most common CDG worldwide, research made great strides, but nearly all of them are still missing a cure. CDG diagnosis has been at a rapid pace since the introduction of whole-exome/whole-genome sequencing as a diagnostic tool. Here, we retrace the history of CDG by analyzing all the patents associated with the topic. To this end, we explored the Espacenet database, extracted a list of patents, and then divided them into three major groups: (1) Drugs/therapeutic approaches for CDG, (2) Drug delivery tools for CDG, (3) Diagnostic tools for CDG. Despite the enormous scientific progress experienced in the last 30 years, diagnostic tools, drugs, and biomarkers are still urgently needed.
Topics: Humans; Glycosylation; Narration; Congenital Disorders of Glycosylation; Databases, Factual; Exome
PubMed: 37644541
DOI: 10.1186/s13023-023-02852-w -
Frontiers in Immunology 2023Protein post-translational modification (PTM) is a regulatory mechanism for protein activity modulation, localization, expression, and interactions with other cellular... (Review)
Review
Protein post-translational modification (PTM) is a regulatory mechanism for protein activity modulation, localization, expression, and interactions with other cellular molecules. It involves the addition or removal of specific chemical groups on the amino acid residues of proteins. Its common forms include phosphorylation, ubiquitylation, methylation, and acetylation. Emerging research has highlighted lactylation, succinylation, and glycosylation. PTMs are involved in vital biological processes. The occurrence and development of diseases depends on protein abundance and is regulated by various PTMs. In addition, advancements in tumor immunotherapy have revealed that protein PTM is also involved in the proliferation, activation, and metabolic reprogramming of immune cells in tumor microenvironment. These PTMs play an important role in tumor immunotherapy. In this review, we comprehensively summarize the role of several types of PTMs in tumor immunotherapy. This review could provide new insights and future research directions for tumor immunotherapy.
Topics: Humans; Neoplasms; Protein Processing, Post-Translational; Glycosylation; Phosphorylation; Immunotherapy; Tumor Microenvironment
PubMed: 37675097
DOI: 10.3389/fimmu.2023.1229397 -
Trends in Molecular Medicine Jun 2022Congenital disorders of glycosylation (CDG) are a group of more than 160 inborn errors of metabolism affecting multiple pathways of protein and lipid glycosylation.... (Review)
Review
Congenital disorders of glycosylation (CDG) are a group of more than 160 inborn errors of metabolism affecting multiple pathways of protein and lipid glycosylation. Patients present with a wide range of symptoms and therapies are only available for very few subtypes. Specific nutritional treatment options for certain CDG types include oral supplementation of monosaccharide sugars, manganese, uridine, or pyridoxine. Additional management includes specific diets (i.e., complex carbohydrate or ketogenic diet), iron supplementation, and albumin infusions. We review the dietary management in CDG with a focus on two subgroups: N-linked glycosylation defects and GPI-anchor disorders.
Topics: Congenital Disorders of Glycosylation; Glycosylation; Humans; Lipid Metabolism
PubMed: 35562242
DOI: 10.1016/j.molmed.2022.04.003