scholarly journals Protein Glycosylation Investigated by Mass Spectrometry: An Overview

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 1986
Author(s):  
Anna Illiano ◽  
Gabriella Pinto ◽  
Chiara Melchiorre ◽  
Andrea Carpentieri ◽  
Vincenza Faraco ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Protein Trafficking ◽  
Inflammatory Diseases ◽  
Protein Glycosylation ◽  
Qualitative And Quantitative Analysis ◽  
Post Translational Modification ◽  
Cellular Mechanisms ◽  
Disease States ◽  
Recognition Protein ◽  
The Individual

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.

scholarly journals Role of Protein Glycosylation in Interactions of Medically Relevant Fungi with the Host

2021 ◽  
Vol 7 (10) ◽  
pp. 875
Author(s):  
Manuela Gómez-Gaviria ◽  
Ana P. Vargas-Macías ◽  
Laura C. García-Carnero ◽  
Iván Martínez-Duncker ◽  
Héctor M. Mora-Montes
Keyword(s):  
Protein Trafficking ◽  
Mammalian Cells ◽  
Fungal Infections ◽  
Fungal Species ◽  
Protein Glycosylation ◽  
Amino Acid Side Chain ◽  
Post Translational Modification ◽  
Fungal Cell ◽  
The Relationship

Protein glycosylation is a highly conserved post-translational modification among organisms. It plays fundamental roles in many biological processes, ranging from protein trafficking and cell adhesion to host–pathogen interactions. According to the amino acid side chain atoms to which glycans are linked, protein glycosylation can be divided into two major categories: N-glycosylation and O-glycosylation. However, there are other types of modifications such as the addition of GPI to the C-terminal end of the protein. Besides the importance of glycoproteins in biological functions, they are a major component of the fungal cell wall and plasma membrane and contribute to pathogenicity, virulence, and recognition by the host immunity. Given that this structure is absent in host mammalian cells, it stands as an attractive target for developing selective compounds for the treatment of fungal infections. This review focuses on describing the relationship between protein glycosylation and the host–immune interaction in medically relevant fungal species.

scholarly journals Breaking the Histone Code with Two-Dimensional Partial Covariance Mass Spectrometry

2020 ◽  
Author(s):  
Taran Driver ◽  
Ruediger Pipkorn ◽  
Vitali Averbukh ◽  
Leszek Frasinski ◽  
Jon P. Marangos ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Large Body ◽  
Active Role ◽  
Repeated Measurements ◽  
Charge Ratio ◽  
Two Dimensional ◽  
Post Translational Modification ◽  
Post Translational Modifications ◽  
Single Fragment ◽  
The Individual

<div> <p>A large body of research points to the biological importance of combinatorial post-translational modifications in proteins, such as the active role played by histone modification patterns in the development of cancers, neurodevelopmental disorders, neurodegenerative and other diseases. Nonetheless, our understanding of the precise biological function of different modification patterns is limited by the difficulty of identifying and quantifying different combinatorial isomers in their mixtures as they naturally occur. Tandem mass spectrometry, which infers primary structure from the mass-to-charge ratios of biomolecular fragments, is the preferred method of analysis for proteins and their post-translational modifications. However, the information contained in the mass-to-charge ratios of the individual fragments is frequently insufficient to identify the correct set of modification patterns present in a mixture of combinatorial isomers. This is because no possible single fragment of a combinatorially modified sequence is unique to that sequence in its mass-to-charge ratio. Here we show that the combinatorial post-translational modification problem can be solved by the recently introduced technique of two-dimensional partial covariance mass spectrometry, which provides information about fragment connectivity in a biomolecule by quantifying correlations between the random intensity fluctuations of its fragments, across repeated measurements. Unique fragment-fragment correlations provide the missing link between the non-unique individual fragments to produce unambiguous fingerprints of co-occurring combinatorial isomers, enabling the discovery of biomolecular combinatorial modification patterns by mass spectrometry.</p> </div>

scholarly journals Breaking the Histone Code with Two-Dimensional Partial Covariance Mass Spectrometry

2020 ◽  
Author(s):  
Taran Driver ◽  
Vitali Averbukh ◽  
Leszek Frasinski ◽  
Jon P. Marangos ◽  
Marina Edelson-Averbukh
Keyword(s):  
Mass Spectrometry ◽  
Large Body ◽  
Active Role ◽  
Repeated Measurements ◽  
Charge Ratio ◽  
Two Dimensional ◽  
Post Translational Modification ◽  
Post Translational Modifications ◽  
Single Fragment ◽  
The Individual

<div> <p>A large body of research points to the biological importance of combinatorial post-translational modifications in proteins, such as the active role played by histone modification patterns in the development of cancers, neurodevelopmental disorders, neurodegenerative and other diseases. Nonetheless, our understanding of the precise biological function of different modification patterns is limited by the difficulty of identifying and quantifying different combinatorial isomers in their mixtures as they naturally occur. Tandem mass spectrometry, which infers primary structure from the mass-to-charge ratios of biomolecular fragments, is the preferred method of analysis for proteins and their post-translational modifications. However, the information contained in the mass-to-charge ratios of the individual fragments is frequently insufficient to identify the correct set of modification patterns present in a mixture of combinatorial isomers. This is because no possible single fragment of a combinatorially modified sequence is unique to that sequence in its mass-to-charge ratio. Here we show that the combinatorial post-translational modification problem can be solved by the recently introduced technique of two-dimensional partial covariance mass spectrometry, which provides information about fragment connectivity in a biomolecule by quantifying correlations between the random intensity fluctuations of its fragments, across repeated measurements. Unique fragment-fragment correlations provide the missing link between the non-unique individual fragments to produce unambiguous fingerprints of co-occurring combinatorial isomers, enabling the discovery of biomolecular combinatorial modification patterns by mass spectrometry.</p> </div>

scholarly journals The Close Relationship between the Golgi Trafficking Machinery and Protein Glycosylation

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2652
Author(s):  
Anna Frappaolo ◽  
Angela Karimpour-Ghahnavieh ◽  
Stefano Sechi ◽  
Maria Grazia Giansanti
Keyword(s):  
Inflammatory Diseases ◽  
Vesicle Trafficking ◽  
Protein Glycosylation ◽  
Post Translational Modification ◽  
Pathological Conditions ◽  
Close Relationship ◽  
Secretory Transport ◽  
Molecular Machinery ◽  
Correct Location ◽  
Glycoprotein Glycosylation

Glycosylation is the most common post-translational modification of proteins; it mediates their correct folding and stability, as well as their transport through the secretory transport. Changes in N- and O-linked glycans have been associated with multiple pathological conditions including congenital disorders of glycosylation, inflammatory diseases and cancer. Glycoprotein glycosylation at the Golgi involves the coordinated action of hundreds of glycosyltransferases and glycosidases, which are maintained at the correct location through retrograde vesicle trafficking between Golgi cisternae. In this review, we describe the molecular machinery involved in vesicle trafficking and tethering at the Golgi apparatus and the effects of mutations in the context of glycan biosynthesis and human diseases.

scholarly journals Breaking the Histone Code with Two-Dimensional Partial Covariance Mass Spectrometry

2020 ◽  
Author(s):  
Taran Driver ◽  
Ruediger Pipkorn ◽  
Vitali Averbukh ◽  
Leszek Frasinski ◽  
Jon P. Marangos ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Large Body ◽  
Active Role ◽  
Repeated Measurements ◽  
Charge Ratio ◽  
Two Dimensional ◽  
Post Translational Modification ◽  
Post Translational Modifications ◽  
Single Fragment ◽  
The Individual

<div> <p>A large body of research points to the biological importance of combinatorial post-translational modifications in proteins, such as the active role played by histone modification patterns in the development of cancers, neurodevelopmental disorders, neurodegenerative and other diseases. Nonetheless, our understanding of the precise biological function of different modification patterns is limited by the difficulty of identifying and quantifying different combinatorial isomers in their mixtures as they naturally occur. Tandem mass spectrometry, which infers primary structure from the mass-to-charge ratios of biomolecular fragments, is the preferred method of analysis for proteins and their post-translational modifications. However, the information contained in the mass-to-charge ratios of the individual fragments is frequently insufficient to identify the correct set of modification patterns present in a mixture of combinatorial isomers. This is because no possible single fragment of a combinatorially modified sequence is unique to that sequence in its mass-to-charge ratio. Here we show that the combinatorial post-translational modification problem can be solved by the recently introduced technique of two-dimensional partial covariance mass spectrometry, which provides information about fragment connectivity in a biomolecule by quantifying correlations between the random intensity fluctuations of its fragments, across repeated measurements. Unique fragment-fragment correlations provide the missing link between the non-unique individual fragments to produce unambiguous fingerprints of co-occurring combinatorial isomers, enabling the discovery of biomolecular combinatorial modification patterns by mass spectrometry.</p> </div>

Dicarbonyl derived post-translational modifications: chemistry bridging biology and aging-related disease

2020 ◽  
Vol 64 (1) ◽  
pp. 97-110
Author(s):  
Christian Sibbersen ◽  
Mogens Johannsen
Keyword(s):  
Mass Spectrometry ◽  
Future Research ◽  
Amino Acid Residues ◽  
Post Translational Modification ◽  
Dicarbonyl Compounds ◽  
Protein Targets ◽  
Post Translational Modifications ◽  
Reactive Protein ◽  
Glycation End Products ◽  
Direct Mass Spectrometry

Abstract In living systems, nucleophilic amino acid residues are prone to non-enzymatic post-translational modification by electrophiles. α-Dicarbonyl compounds are a special type of electrophiles that can react irreversibly with lysine, arginine, and cysteine residues via complex mechanisms to form post-translational modifications known as advanced glycation end-products (AGEs). Glyoxal, methylglyoxal, and 3-deoxyglucosone are the major endogenous dicarbonyls, with methylglyoxal being the most well-studied. There are several routes that lead to the formation of dicarbonyl compounds, most originating from glucose and glucose metabolism, such as the non-enzymatic decomposition of glycolytic intermediates and fructosyl amines. Although dicarbonyls are removed continuously mainly via the glyoxalase system, several conditions lead to an increase in dicarbonyl concentration and thereby AGE formation. AGEs have been implicated in diabetes and aging-related diseases, and for this reason the elucidation of their structure as well as protein targets is of great interest. Though the dicarbonyls and reactive protein side chains are of relatively simple nature, the structures of the adducts as well as their mechanism of formation are not that trivial. Furthermore, detection of sites of modification can be demanding and current best practices rely on either direct mass spectrometry or various methods of enrichment based on antibodies or click chemistry followed by mass spectrometry. Future research into the structure of these adducts and protein targets of dicarbonyl compounds may improve the understanding of how the mechanisms of diabetes and aging-related physiological damage occur.

Natural Products for Regulating Macrophages M2 Polarization

2020 ◽  
Vol 15 (7) ◽  
pp. 559-569 ◽  
Author(s):  
Zhen Chang ◽  
Youhan Wang ◽  
Chang Liu ◽  
Wanli Smith ◽  
Lingbo Kong
Keyword(s):  
Molecular Mechanisms ◽  
Inflammatory Diseases ◽  
Therapeutic Strategies ◽  
Research Progress ◽  
Cellular Mechanisms ◽  
Pharmacological Activities ◽  
Current Review ◽  
M2 Polarization ◽  
Macrophages Polarization ◽  
Herbal Plants

Macrophages M2 polarization have been taken as an anti-inflammatory progression during inflammation. Natural plant-derived products, with potential therapeutic and preventive activities against inflammatory diseases, have received increasing attention in recent years because of their whole regulative effects and specific pharmacological activities. However, the molecular mechanisms about how different kinds of natural compounds regulate macrophages polarization still unclear. Therefore, in the current review, we summarized the detailed research progress on the active compounds derived from herbal plants with regulating effects on macrophages, especially M2 polarization. These natural occurring compounds including flavonoids, terpenoids, glycosides, lignans, coumarins, alkaloids, polyphenols and quinones. In addition, we extensively discussed the cellular mechanisms underlying the M2 polarization for each compound, which could provide potential therapeutic strategies aiming macrophages M2 polarization.

scholarly journals N-Terminomics Strategies for Protease Substrates Profiling

Molecules ◽  
2021 ◽  
Vol 26 (15) ◽  
pp. 4699
Author(s):  
Mubashir Mintoo ◽  
Amritangshu Chakravarty ◽  
Ronak Tilvawala
Keyword(s):  
Mass Spectrometry ◽  
Protease Activity ◽  
Viral Infections ◽  
Mass Spectrometry Analysis ◽  
Post Translational Modification ◽  
Spectrometry Analysis ◽  
Physiological Conditions ◽  
Inflammatory Conditions ◽  
Biological Mixtures

Proteases play a central role in various biochemical pathways catalyzing and regulating key biological events. Proteases catalyze an irreversible post-translational modification called proteolysis by hydrolyzing peptide bonds in proteins. Given the destructive potential of proteolysis, protease activity is tightly regulated. Dysregulation of protease activity has been reported in numerous disease conditions, including cancers, neurodegenerative diseases, inflammatory conditions, cardiovascular diseases, and viral infections. The proteolytic profile of a cell, tissue, or organ is governed by protease activation, activity, and substrate specificity. Thus, identifying protease substrates and proteolytic events under physiological conditions can provide crucial information about how the change in protease regulation can alter the cellular proteolytic landscape. In recent years, mass spectrometry-based techniques called N-terminomics have become instrumental in identifying protease substrates from complex biological mixtures. N-terminomics employs the labeling and enrichment of native and neo-N-termini peptides, generated upon proteolysis followed by mass spectrometry analysis allowing protease substrate profiling directly from biological samples. In this review, we provide a brief overview of N-terminomics techniques, focusing on their strengths, weaknesses, limitations, and providing specific examples where they were successfully employed to identify protease substrates in vivo and under physiological conditions. In addition, we explore the current trends in the protease field and the potential for future developments.

Compositional Analysis of Organosolv Poplar Lignin by Using High-Performance Liquid Chromatography/High-resolution Multi-stage Tandem Mass Spectrometry

2021 ◽  
Author(s):  
Jifa Zhang ◽  
Yuan Jiang ◽  
Leah F Easterling ◽  
Anton Anster ◽  
Wanru Li ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
High Performance ◽  
Compositional Analysis ◽  
Complex Mixtures ◽  
Tandem Mass ◽  
Multi Stage ◽  
The Individual ◽  
Environmentally Friendly Process

Organosolv treatment is an efficient and environmentally friendly process to degrade lignin into small compounds. The capability of characterizing the individual compounds in the complex mixtures formed upon organosolv treatment...

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