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Recent Advances in Glycoproteomics: Theory, Methods and Applications

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (15 November 2022) | Viewed by 13796

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Special Issue Editor

Dr. Hans J.C.T. Wessels

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Guest Editor

Translational Metabolic Laboratory, Department of Laboratory Medicine, Radboud University Medical Center Geert Grooteplein Zuid 10, 6525 GA Nijmegen, The Netherlands
Interests: protein glycosylation; mitochondrial disease; proteoforms; proteomics; mass spectrometry; ion mobility
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Protein glycosylation is a key mediator of protein biology and a major contributor to protein diversity in bacteria, archaea, and eukaryota. Glycoprotein characterization by mass spectrometry has become a powerful tool to elucidate glycan structures on proteins and to investigate alterations in the glycosylation status of proteins in response to cellular changes. Aberrant protein glycosylation has been linked to various genetic and acquired human diseases, which provides exciting opportunities for biomarker applications and rationale treatment strategies that modulate protein glycosylation. Comprehensive analytical characterization of glycoproteins is also of great interest in (glyco)biology, healthcare, and biotechnology.

Recent developments in mass-spectrometry-based glycoproteomics have enabled in-depth characterization of the glycan micro-heterogeneity (different glycan structures on a singly glycosylation site) and macro-heterogeneity (different combinations of glycan structures on a single protein molecule) for proteins in both simple and complex matrices.

This Special Issue aims to provide essential background information and application examples to both glycoproteomics scientists and non-experts. We look for manuscripts to cover glycobiology, glycoproteomics technology, and glycoproteomics applications in biological research, healthcare, and industry. Both review and article manuscript types that focus on any of the topics listed are welcomed.

Dr. Hans J.C.T. Wessels
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

glycobiology
protein glycosylation
glycoengineering
glycoproteomics
glycoproteins
glycopeptides
glycan

Published Papers (5 papers)

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Research

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16 pages, 3392 KiB

Open AccessArticle

The GlycoPaSER Prototype as a Real-Time N-Glycopeptide Identification Tool Based on the PaSER Parallel Computing Platform

by Gad Armony, Sven Brehmer, Tharan Srikumar, Lennard Pfennig, Fokje Zijlstra, Dennis Trede, Gary Kruppa, Dirk J. Lefeber, Alain J. van Gool and Hans J. C. T. Wessels

Int. J. Mol. Sci. 2023, 24(9), 7869; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24097869 - 26 Apr 2023

Cited by 2 | Viewed by 1978

Abstract

Real-time database searching allows for simpler and automated proteomics workflows as it eliminates technical bottlenecks in high-throughput experiments. Most importantly, it enables results-dependent acquisition (RDA), where search results can be used to guide data acquisition during acquisition. This is especially beneficial for glycoproteomics since the wide range of physicochemical properties of glycopeptides lead to a wide range of optimal acquisition parameters. We established here the GlycoPaSER prototype by extending the Parallel Search Engine in Real-time (PaSER) functionality for real-time glycopeptide identification from fragmentation spectra. Glycopeptide fragmentation spectra were decomposed into peptide and glycan moiety spectra using common N-glycan fragments. Each moiety was subsequently identified by a specialized algorithm running in real-time. GlycoPaSER can keep up with the rate of data acquisition for real-time analysis with similar performance to other glycoproteomics software and produces results that are in line with the literature reference data. The GlycoPaSER prototype presented here provides the first proof-of-concept for real-time glycopeptide identification that unlocks the future development of RDA technology to transcend data acquisition. Full article

(This article belongs to the Special Issue Recent Advances in Glycoproteomics: Theory, Methods and Applications)

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17 pages, 3298 KiB

Open AccessArticle

Glycoproteomics in Cerebrospinal Fluid Reveals Brain-Specific Glycosylation Changes

by Melissa Baerenfaenger, Merel A. Post, Pieter Langerhorst, Karin Huijben, Fokje Zijlstra, Joannes F. M. Jacobs, Marcel M. Verbeek, Hans J. C. T. Wessels and Dirk J. Lefeber

Int. J. Mol. Sci. 2023, 24(3), 1937; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24031937 - 18 Jan 2023

Cited by 3 | Viewed by 2115

Abstract

The glycosylation of proteins plays an important role in neurological development and disease. Glycoproteomic studies on cerebrospinal fluid (CSF) are a valuable tool to gain insight into brain glycosylation and its changes in disease. However, it is important to consider that most proteins in CSFs originate from the blood and enter the CSF across the blood–CSF barrier, thus not reflecting the glycosylation status of the brain. Here, we apply a glycoproteomics method to human CSF, focusing on differences between brain- and blood-derived proteins. To facilitate the analysis of the glycan site occupancy, we refrain from glycopeptide enrichment. In healthy individuals, we describe the presence of heterogeneous brain-type N-glycans on prostaglandin H2-D isomerase alongside the dominant plasma-type N-glycans for proteins such as transferrin or haptoglobin, showing the tissue specificity of protein glycosylation. We apply our methodology to patients diagnosed with various genetic glycosylation disorders who have neurological impairments. In patients with severe glycosylation alterations, we observe that heavily truncated glycans and a complete loss of glycans are more pronounced in brain-derived proteins. We speculate that a similar effect can be observed in other neurological diseases where a focus on brain-derived proteins in the CSF could be similarly beneficial to gain insight into disease-related changes. Full article

(This article belongs to the Special Issue Recent Advances in Glycoproteomics: Theory, Methods and Applications)

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11 pages, 3684 KiB

Open AccessArticle

BOA/DHB/Na: An Efficient UV-MALDI Matrix for High-Sensitivity and Auto-Tagging Glycomics

by Erina Barada and Hiroshi Hinou

Int. J. Mol. Sci. 2022, 23(20), 12510; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232012510 - 19 Oct 2022

Cited by 5 | Viewed by 1994

Abstract

Matrix selection is a critical factor for success in glycomics studies using matrix-assisted laser desorption/ionization–mass spectrometry (MALDI–MS). In this study, we evaluated and optimized a new solid ionic matrix—O-benzylhydroxylamine (BOA)/2,5-dihydroxybenzoic acid (DHB)/Na—containing BOA and a small amount of sodium as the counter salt of DHB. The concentration of a mixture of BOA/DHB/Na and glycans on a MALDI target plate led to O-benzyloxy tagging of the reducing ends of the glycans. The BOA/DHB/Na matrix showed excellent aggregation performance and the ability to form a homogeneous solid salt on the MALDI target plate with a water-repellent surface. In addition, the BOA/DHB/Na matrix showed a simple peak pattern with suppressed in-source and post-source decay of the reducing ends of the glycans, as well as improved ionization efficiency of glycans. Utilizing the characteristics of the BOA/DHB/Na matrix, O-glycan analysis of porcine stomach mucin showed excellent detection sensitivity and reproducibility of the peak patterns. This BOA/DHB/Na matrix can accelerate glycomics studies using MALDI–MS and, in combination with other organic salt-type matrices that we have developed, constitutes a valuable tool for glycomics studies. Full article

(This article belongs to the Special Issue Recent Advances in Glycoproteomics: Theory, Methods and Applications)

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17 pages, 4816 KiB

Open AccessArticle

Definition of IgG Subclass-Specific Glycopatterns in Idiopathic Membranous Nephropathy: Aberrant IgG Glycoforms in Blood

by Clizia Chinello, Noortje de Haan, Giulia Capitoli, Barbara Trezzi, Antonella Radice, Lisa Pagani, Lucrezia Criscuolo, Stefano Signorini, Stefania Galimberti, Renato Alberto Sinico, Manfred Wuhrer and Fulvio Magni

Int. J. Mol. Sci. 2022, 23(9), 4664; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23094664 - 23 Apr 2022

Cited by 7 | Viewed by 2402

Abstract

The podocyte injury, and consequent proteinuria, that characterize the pathology of idiopathic membranous nephropathy (IMN) is mediated by an autoimmune reaction against podocyte antigens. In particular, the activation of pathways leading to abundant renal deposits of complement is likely to involve the binding of mannose-binding lectin (MBL) to aberrant glycans on immunoglobulins. To obtain a landscape of circulatory IgG Fc glycosylation characterizing this disease, we conducted a systematic N-glycan profiling study of IgG1, 2, and 4 by mass spectrometry. The cohort included 57 IMN patients, a pathological control group with nephrotic syndrome (PN) (n = 20), and 88 healthy control subjects. The effect of sex and age was assessed in all groups and controlled by rigorous matching. Several IgG Fc glycan traits were found to be associated with IMN. Interestingly, among them, only IgG4-related results were specific for IMN and not for PN. Hypo-galactosylation of IgG4, already shown for IMN, was observed to occur in the absence of core fucose, in line with a probable increase of pro-inflammatory IgG. In addition, elevated levels of fucosylated IgG4, along with low levels of hybrid-type glycans, were detected. Some of these IgG4 alterations are likely to be more pronounced in high PLA2R (phospholipase A2 receptor) patients. IgG Fc glycosylation patterns associated with IMN warrant further studies of their role in disease mechanisms and may eventually enrich the diagnostic spectrum regarding patient stratification. Full article

(This article belongs to the Special Issue Recent Advances in Glycoproteomics: Theory, Methods and Applications)

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Review

Jump to: Research

25 pages, 2041 KiB

Open AccessReview

Strategies for Proteome-Wide Quantification of Glycosylation Macro- and Micro-Heterogeneity

by Pan Fang, Yanlong Ji, Thomas Oellerich, Henning Urlaub and Kuan-Ting Pan

Int. J. Mol. Sci. 2022, 23(3), 1609; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23031609 - 30 Jan 2022

Cited by 8 | Viewed by 4406

Abstract

Protein glycosylation governs key physiological and pathological processes in human cells. Aberrant glycosylation is thus closely associated with disease progression. Mass spectrometry (MS)-based glycoproteomics has emerged as an indispensable tool for investigating glycosylation changes in biological samples with high sensitivity. Following rapid improvements in methodologies for reliable intact glycopeptide identification, site-specific quantification of glycopeptide macro- and micro-heterogeneity at the proteome scale has become an urgent need for exploring glycosylation regulations. Here, we summarize recent advances in N- and O-linked glycoproteomic quantification strategies and discuss their limitations. We further describe a strategy to propagate MS data for multilayered glycopeptide quantification, enabling a more comprehensive examination of global and site-specific glycosylation changes. Altogether, we show how quantitative glycoproteomics methods explore glycosylation regulation in human diseases and promote the discovery of biomarkers and therapeutic targets. Full article

(This article belongs to the Special Issue Recent Advances in Glycoproteomics: Theory, Methods and Applications)

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