-
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 -
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 -
Ageing Research Reviews Aug 2023Glycosylation is a common post-translational modification of brain proteins including cell surface adhesion molecules, synaptic proteins, receptors and channels, as well... (Review)
Review
Glycosylation is a common post-translational modification of brain proteins including cell surface adhesion molecules, synaptic proteins, receptors and channels, as well as intracellular proteins, with implications in brain development and functions. Using advanced state-of-the-art glycomics and glycoproteomics technologies in conjunction with glycoinformatics resources, characteristic glycosylation profiles in brain tissues are increasingly reported in the literature and growing evidence shows deregulation of glycosylation in central nervous system disorders, including aging associated neurodegenerative diseases. Glycan signatures characteristic of brain tissue are also frequently described in cerebrospinal fluid due to its enrichment in brain-derived molecules. A detailed structural analysis of brain and cerebrospinal fluid glycans collected in publications in healthy and neurodegenerative conditions was undertaken and data was compiled to create a browsable dedicated set in the GlyConnect database of glycoproteins (https://glyconnect.expasy.org/brain). The shared molecular composition of cerebrospinal fluid with brain enhances the likelihood of novel glycobiomarker discovery for neurodegeneration, which may aid in unveiling disease mechanisms, therefore, providing with novel therapeutic targets as well as diagnostic and progression monitoring tools.
Topics: Humans; Glycosylation; Neurodegenerative Diseases; Glycoproteins; Protein Processing, Post-Translational; Glycomics; Polysaccharides; Biomarkers
PubMed: 37348818
DOI: 10.1016/j.arr.2023.101991 -
International Journal of Molecular... May 2021Aberrant glycosylation has long been known to be associated with cancer, since it is involved in key mechanisms such as tumour onset, development and progression. This... (Review)
Review
Aberrant glycosylation has long been known to be associated with cancer, since it is involved in key mechanisms such as tumour onset, development and progression. This review will focus on protein glycosylation studies in cells, tissue, urine and serum in the context of prostate cancer. A dedicated section will cover the glycoforms of prostate specific antigen, the molecule that, despite some important limitations, is routinely tested for helping prostate cancer diagnosis. Our aim is to provide readers with an overview of mass spectrometry-based glycoproteomics of prostate cancer. From this perspective, the first part of this review will illustrate the main strategies for glycopeptide enrichment and mass spectrometric analysis. The molecular information obtained by glycoproteomic analysis performed by mass spectrometry has led to new insights into the mechanism linking aberrant glycosylation to cancer cell proliferation, migration and immunoescape.
Topics: Biomarkers, Tumor; Glycosylation; Humans; Male; Mass Spectrometry; Prostate-Specific Antigen; Prostatic Neoplasms; Proteomics
PubMed: 34069262
DOI: 10.3390/ijms22105222 -
Oncogene Jun 2023Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. Understanding the cancer mechanisms provides novel diagnostic, prognostic, and... (Review)
Review
Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. Understanding the cancer mechanisms provides novel diagnostic, prognostic, and therapeutic markers for the management of HCC disease. In addition to genomic and epigenomic regulation, post-translational modification exerts a profound influence on protein functions and plays a critical role in regulating various biological processes. Protein glycosylation is one of the most common and complex post-translational modifications of newly synthesized proteins and acts as an important regulatory mechanism that is implicated in fundamental molecular and cell biology processes. Recent studies in glycobiology suggest that aberrant protein glycosylation in hepatocytes contributes to the malignant transformation to HCC by modulating a wide range of pro-tumorigenic signaling pathways. The dysregulated protein glycosylation regulates cancer growth, metastasis, stemness, immune evasion, and therapy resistance, and is regarded as a hallmark of HCC. Changes in protein glycosylation could serve as potential diagnostic, prognostic, and therapeutic factors in HCC. In this review, we summarize the functional importance, molecular mechanism, and clinical application of protein glycosylation alterations in HCC.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Glycosylation; Protein Processing, Post-Translational; Carcinogenesis; Proteins
PubMed: 37193819
DOI: 10.1038/s41388-023-02702-w -
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 2021Advances in nuclease-based gene-editing technologies have enabled precise, stable, and systematic genetic engineering of glycosylation capacities in mammalian cells,... (Review)
Review
Advances in nuclease-based gene-editing technologies have enabled precise, stable, and systematic genetic engineering of glycosylation capacities in mammalian cells, opening up a plethora of opportunities for studying the glycome and exploiting glycans in biomedicine. Glycoengineering using chemical, enzymatic, and genetic approaches has a long history, and precise gene editing provides a nearly unlimited playground for stable engineering of glycosylation in mammalian cells to explore and dissect the glycome and its many biological functions. Genetic engineering of glycosylation in cells also brings studies of the glycome to the single cell level and opens up wider use and integration of data in traditional omics workflows in cell biology. The last few years have seen new applications of glycoengineering in mammalian cells with perspectives for wider use in basic and applied glycosciences, and these have already led to discoveries of functions of glycans and improved designs of glycoprotein therapeutics. Here, we review the current state of the art of genetic glycoengineering in mammalian cells and highlight emerging opportunities.
Topics: Animals; Gene Editing; Gene Expression Regulation; Gene Knockdown Techniques; Genetic Engineering; Glycoproteins; Glycosylation; Humans; Mammals; Polysaccharides
PubMed: 33617880
DOI: 10.1016/j.jbc.2021.100448 -
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