-
Journal of Proteome Research Oct 2020Glycosylation is one of the most important post-translational modifications of proteins and plays an essential role in spermatogenesis, maturation, extracellular quality... (Review)
Review
Glycosylation is one of the most important post-translational modifications of proteins and plays an essential role in spermatogenesis, maturation, extracellular quality control, capacitation, sperm-egg recognition, and final fertilization. Spermatozoa are synthesized in the testes inactively with a thick glycocalyx and passed through the epididymis for further modification by glycosylation, deglycosylation, and integration to reach maturation. Subsequently, sperm capacitation and further fertilization require redistribution of glycoconjugates and dramatic glycocalyx modification of the spermatozoa surface. Furthermore, glycoproteins and glycans in seminal plasma are functional in maintaining spermatozoa structure and stability. Therefore, aberrant glycosylation may cause alteration of semen function and even infertility. Currently, mass spectrometry-based technologies have allowed large-scale profiling of glycans and glycoproteins in human semen. Quantitative analysis of semen glycosylation has also indicated many involved glycoproteome issues in male infertility and the potential biomarkers for diagnosis of male infertility in clinical. This review summarizes the role of glycosylation during spermatozoa development, the large-scale profiling of glycome and glycoproteome in human semen, as well as the association of aberrant glycosylation with infertility.
Topics: Epididymis; Glycosylation; Humans; Infertility, Male; Male; Semen; Spermatozoa
PubMed: 32875803
DOI: 10.1021/acs.jproteome.9b00795 -
Biomolecules Feb 2024Glycosylation, a prevalent post-translational modification, plays a pivotal role in regulating intricate cellular processes by covalently attaching glycans to... (Review)
Review
Glycosylation, a prevalent post-translational modification, plays a pivotal role in regulating intricate cellular processes by covalently attaching glycans to macromolecules. Dysregulated glycosylation is linked to a spectrum of diseases, encompassing cancer, neurodegenerative disorders, congenital disorders, infections, and inflammation. This review delves into the intricate interplay between glycosylation and protein conformation, with a specific focus on the profound impact of N-glycans on the selection of distinct protein conformations characterized by distinct interactomes-namely, protein assemblies-under normal and pathological conditions across various diseases. We begin by examining the spike protein of the SARS virus, illustrating how N-glycans regulate the infectivity of pathogenic agents. Subsequently, we utilize the prion protein and the chaperone glucose-regulated protein 94 as examples, exploring instances where N-glycosylation transforms physiological protein structures into disease-associated forms. Unraveling these connections provides valuable insights into potential therapeutic avenues and a deeper comprehension of the molecular intricacies that underlie disease conditions. This exploration of glycosylation's influence on protein conformation effectively bridges the gap between the glycome and disease, offering a comprehensive perspective on the therapeutic implications of targeting conformational mutants and their pathologic assemblies in various diseases. The goal is to unravel the nuances of these post-translational modifications, shedding light on how they contribute to the intricate interplay between protein conformation, assembly, and disease.
Topics: Glycosylation; Protein Processing, Post-Translational; Polysaccharides; Protein Conformation; Prions
PubMed: 38540703
DOI: 10.3390/biom14030282 -
Current Opinion in Biotechnology Oct 2021Protein glycosylation is the most diverse and omnipresent protein modification. Glycosylation provides glycoproteins with important structural and functional properties... (Review)
Review
Protein glycosylation is the most diverse and omnipresent protein modification. Glycosylation provides glycoproteins with important structural and functional properties to facilitate critical biological processes. Despite the significance of protein glycosylation, the investigation of glycoproteome, especially O-linked glycoproteome, remains elusive due to the lack of a comprehensive methodology to conform with the diversity of O-linked glycoforms of O-linked glycoproteins. In recent years, mass spectrometry has become an indispensable tool for the characterization of O-linked glycosylated proteins across biological systems. We herein highlight the recent developments in MS-based O-linked glycoproteomic technologies, quantitative data acquisition strategy and bioinformatic tools, with a special focus on mucin-type O-linked glycosylation.
Topics: Glycoproteins; Glycosylation; Protein Processing, Post-Translational; Proteome
PubMed: 34358979
DOI: 10.1016/j.copbio.2021.07.006 -
Advances in Carbohydrate Chemistry and... 2022In the post-genomic era, post- and co-translational modifications (P/C-TM) of proteins are known as the more essential elements for the activation of protein function.... (Review)
Review
In the post-genomic era, post- and co-translational modifications (P/C-TM) of proteins are known as the more essential elements for the activation of protein function. Among these protein modifications, glycosylation is one of the most abundant modifications in eukaryotic cells. The synthesis of glycoproteins with uniform glycan structures is essential for functional analysis of glycoproteins and biochemical research. For that purpose, chemical methods to synthesize glycoproteins with chemically uniform glycan structures have been developed. In this review, we highlight our recent advances in the preparation of homogeneous glycoproteins. Especially, we introduce both semi-synthesis and chemical synthesis of glycoproteins along with semi-synthesis of various complex-type N-glycans for the solid-phase synthesis of glycopeptide-thioesters.
Topics: Glycoproteins; Polysaccharides; Glycosylation; Glycopeptides; Protein Processing, Post-Translational
PubMed: 36435534
DOI: 10.1016/bs.accb.2022.09.004 -
Current Opinion in Biotechnology Dec 2022The commercial value of specialty carbohydrates and glycosylated compounds has sparked considerable interest in the synthetic potential of carbohydrate-active enzymes... (Review)
Review
The commercial value of specialty carbohydrates and glycosylated compounds has sparked considerable interest in the synthetic potential of carbohydrate-active enzymes (CAZymes). Protein engineering methods have proven to be highly successful in expanding the range of glycosylation reactions that these enzymes can perform efficiently and cost-effectively. The past few years have witnessed meaningful progress in this area, largely due to a sharper focus on the understanding of structure-function relationships and mechanistic intricacies. Here, we summarize recent studies that demonstrate how protein engineers have become much better at traversing the fitness landscape of CAZymes through mutational bridges that connect the different activity types.
Topics: Carbohydrates; Glycosylation; Proteins; Enzymes
PubMed: 36156353
DOI: 10.1016/j.copbio.2022.102804 -
Journal of Proteome Research Jun 2023Glycosylation is one of the most common and important protein modifications, and it regulates the properties and functions of a wide range of proteins. Aberrant... (Review)
Review
Glycosylation is one of the most common and important protein modifications, and it regulates the properties and functions of a wide range of proteins. Aberrant glycosylation is directly related to human diseases. Recently, with the advancement of mass spectrometry (MS) instrumentation and MS-based glycoproteomic methods, global characterization of glycoproteins in complex biological samples has become possible. Using quantitative proteomics, the abundance of glycoproteins in different samples can be quantified, which provides a wealth of information to further our understanding of protein functions, cellular activities, and the molecular mechanisms of diseases. In this review, we discuss quantitative proteomic methods used for comprehensive analysis of protein glycosylation, and cover the applications of quantitative glycoproteomics to unveil the properties and functions of glycoproteins and their association with various diseases. It is expected that quantitative proteomic methods will be extensively applied to explore the role of protein glycosylation in complex biological systems, and to identify glycoproteins as biomarkers for disease detection and as therapeutic targets for disease treatment.
Topics: Humans; Proteomics; Glycoproteins; Glycosylation; Protein Processing, Post-Translational; Mass Spectrometry
PubMed: 37010087
DOI: 10.1021/acs.jproteome.3c00015 -
Mass Spectrometry Reviews Aug 2019Protein glycosylation is ubiquitous in biological systems and plays essential roles in many cellular events. Global and site-specific analysis of glycoproteins in... (Review)
Review
Protein glycosylation is ubiquitous in biological systems and plays essential roles in many cellular events. Global and site-specific analysis of glycoproteins in complex biological samples can advance our understanding of glycoprotein functions and cellular activities. However, it is extraordinarily challenging because of the low abundance of many glycoproteins and the heterogeneity of glycan structures. The emergence of mass spectrometry (MS)-based proteomics has provided us an excellent opportunity to comprehensively study proteins and their modifications, including glycosylation. In this review, we first summarize major methods for glycopeptide/glycoprotein enrichment, followed by the chemical and enzymatic methods to generate a mass tag for glycosylation site identification. We next discuss the systematic and quantitative analysis of glycoprotein dynamics. Reversible protein glycosylation is dynamic, and systematic study of glycoprotein dynamics helps us gain insight into glycoprotein functions. The last part of this review focuses on the applications of MS-based proteomics to study glycoproteins in different biological systems, including yeasts, plants, mice, human cells, and clinical samples. Intact glycopeptide analysis is also included in this section. Because of the importance of glycoproteins in complex biological systems, the field of glycoproteomics will continue to grow in the next decade. Innovative and effective MS-based methods will exponentially advance glycoscience, and enable us to identify glycoproteins as effective biomarkers for disease detection and drug targets for disease treatment. © 2019 Wiley Periodicals, Inc. Mass Spec Rev 9999: XX-XX, 2019.
Topics: Animals; Glycomics; Glycopeptides; Glycoproteins; Glycosylation; Humans; Mass Spectrometry; Polysaccharides; Proteomics
PubMed: 30605224
DOI: 10.1002/mas.21586 -
Frontiers in Cellular and Infection... 2020In recent years, protein glycosylation in pathogenic bacteria has attracted more and more attention, and accumulating evidence indicated that this type of... (Review)
Review
In recent years, protein glycosylation in pathogenic bacteria has attracted more and more attention, and accumulating evidence indicated that this type of posttranslational modification is involved in many physiological processes. The NleB from several enteropathogenic bacteria species as well as SseK from are type III secretion system effectors, which have an atypical N-acetylglucosamine (N-GlcNAc) transferase activity that specifically modified a conserved arginine in TRADD, FADD, and RIPK1. NleB/SseKs GlcNAcylation of death domain proteins abrogates homotypic and heterotypic death receptors/adaptors interactions, thereby blocking an important antimicrobial host response. Interestingly, NleB/SseKs could also GlcNAcylate themselves, and self-GlcNAcylation of NleB, SseK1, and SseK3 are crucial for their biological activity during infection. In addition, EarP (EF-P specific arginine rhamnosyl transferase for Posttranslational activation) catalyzes arginine rhamnosylation of translation elongation factor P (EF-P). Importantly, this kind of N-linked protein glycosylation is not only important for EF-P dependent rescue of polyproline stalled ribosomes but also for pathogenicity in and other clinically relevant bacteria. Glycosylation of arginine is unique because the guanidine group of arginine has a high acid dissociation constant value and representing an extremely poor nucleophile. Recently, the crystal structures of NleB, SseKs, EarP, arginine GlcNAcylated death domain-containing proteins, NleB/FADD-DD, and EarP/EF-P/dTDP-β-L-rhamnose were solved by our group and other groups, revealing the unique catalytic mechanisms. In this review, we provide detailed information about the currently known arginine glycosyltransferases and their potential catalytic mechanisms.
Topics: Arginine; Bacterial Proteins; Catalysis; Fas-Associated Death Domain Protein; Glycosylation; Pseudomonas aeruginosa; Receptor-Interacting Protein Serine-Threonine Kinases; TNF Receptor-Associated Death Domain Protein
PubMed: 32411621
DOI: 10.3389/fcimb.2020.00185 -
Clinical & Translational Oncology :... Oct 2022Endometrial cancer (EC) is one of the most common tumors in the female reproductive system, which seriously threatens women's health, particularly in developed... (Review)
Review
Endometrial cancer (EC) is one of the most common tumors in the female reproductive system, which seriously threatens women's health, particularly in developed countries. 13% of the patients with EC have a poor prognosis due to recurrence and metastasis. Therefore, identifying good predictive biomarkers and therapeutic targets is critical to enable the early detection of metastasis and improve the prognosis. For decades, extensive studies had focused on glycans and glycoproteins in the progression of cancer. The types of glycans that are covalently attached to the polypeptide backbone, usually via nitrogen or oxygen linkages, are known as N‑glycans or O‑glycans, respectively. The degree of protein glycosylation and the aberrant changes in the carbohydrate structures have been implicated in the extent of tumorigenesis and reported to play a critical role in regulating tumor invasion, metabolism, and immunity. This review summarizes the essential biological role of glycosylation in EC, with a focus on the recent advances in glycomics and glycosylation markers, highlighting their implications in the diagnosis and treatment of EC.
Topics: Biomarkers; Endometrial Neoplasms; Female; Glycomics; Glycoproteins; Glycosylation; Humans; Polysaccharides
PubMed: 35752750
DOI: 10.1007/s12094-022-02858-z -
Advances in Experimental Medicine and... 2023De novo synthesis of dolichol (Dol) and dolichyl phosphate (Dol-P) is essential for protein glycosylation. Herein, we provide a brief overview of Dol and Dol-P synthesis... (Review)
Review
De novo synthesis of dolichol (Dol) and dolichyl phosphate (Dol-P) is essential for protein glycosylation. Herein, we provide a brief overview of Dol and Dol-P synthesis and the maintenance of their cellular content. Retinal Dol metabolism and the requirement of Dol-linked oligosaccharide synthesis in the neural retina also are discussed. There are recently discovered and an emerging class of rare congenital disorders that affect Dol metabolism, involving the genes DHDDS, NUS1, SRD5A3, and DOLK. Further understanding of these congenital disorders is evolving, based upon studies utilizing yeast and murine models, as well as clinical reports of these rare disorders. We summarize the known visual deficits associated with Dol metabolism disorders, and identify the need for generation and characterization of suitable animal models of these disorders to elucidate the underlying molecular and cellular mechanisms of the associated retinopathies.
Topics: Animals; Mice; Dolichols; Glycosylation; Oligosaccharides; Retina; Saccharomyces cerevisiae
PubMed: 37440071
DOI: 10.1007/978-3-031-27681-1_66