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Protein–Carbohydrate Interactions: Structure–Function Relationships

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (30 November 2018) | Viewed by 37944

Special Issue Editors


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Guest Editor
Department of Biotechnology, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000 Ghent, Belgium
Interests: lectins; carbohydrate-binding proteins; protein–carbohydrate interactions; carbohydrate recognition; glycosylation; biological activity; physiological importance; defense and immunity; stress proteins; glycobiology
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Guest Editor
Institut de Recherche et Développement, Faculté de Pharmacie, UMR 152 PharmaDev, Université Paul Sabatier, 35 Chemin des Maraîchers, 31062 Toulouse, France
Interests: food allergy; allergens; epitopes; celiac disease; structural approaches
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Glycobiology encompasses the study of the structure, function and biology of carbohydrates. These carbohydrate structures are present at the cell surface, as part of a membrane glycoproteins or glycolipids, in cell walls, or can also be available as free carbohydrates inside the cell. The field of glycobiology is growing fast, especially since it was shown that carbohydrate interactions play an important role in many biological processes and are of interest for biomedical and biomolecular research, and the applications emerging from it.

Protein–carbohydrate interactions underlie many important biological events, including cellular signaling, development, infection processes, stress responses, communication between cells and organisms. One major group of carbohydrate-binding proteins is the family of lectins. Proteins can be considered lectins if they contain at least one lectin domain, allowing them to recognize and bind carbohydrates or glycan structures in a specific and reversible way. The large group of lectins is quite heterogeneous and can be subdivided in different lectin families, each typified by a specific carbohydrate recognition domain. The diversity within the group is also illustrated by the fact that a particular carbohydrate-recognition domain can recognize different carbohydrate structures, or lectins belonging to a particular family can be located in diverse locations in a plant cell.

Although there is strong evidence for the importance of protein-carbohydrate interactions in plants and vertebrates, little is known on the implications of the interaction for growth and development. In this Special Issue we aim to collect manuscripts from different research disciplines covering the current knowledge of “Protein–Carbohydrate Interactions” and their importance for biological processes, the structure–function relationships, and their applications in biochemistry, biotechnology, and biomedicine.

Prof. Dr. Els Van Damme
Prof. Dr. Pierre Rougé
Guest Editors

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Keywords

  • lectins
  • carbohydrates
  • glycans
  • protein-carbohydrate interactions
  • structure-function relationships
  • applications
  • glycobiology
  • biotechnology
  • biochemistry
  • medical applications

Published Papers (6 papers)

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Research

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19 pages, 3863 KiB  
Article
Recombinant Glycoprotein E of Varicella Zoster Virus Contains Glycan-Peptide Motifs That Modulate B Cell Epitopes into Discrete Immunological Signatures
by Rickard Nordén, Jonas Nilsson, Ebba Samuelsson, Christian Risinger, Carina Sihlbom, Ola Blixt, Göran Larson, Sigvard Olofsson and Tomas Bergström
Int. J. Mol. Sci. 2019, 20(4), 954; https://doi.org/10.3390/ijms20040954 - 22 Feb 2019
Cited by 15 | Viewed by 8097
Abstract
A recombinant subunit vaccine (Shingrix®) was recently licensed for use against herpes zoster. This vaccine is based on glycoprotein E (gE) of varicella zoster virus (VZV), the most abundantly expressed protein of VZV, harboring sites for N- and O-linked glycosylation. The [...] Read more.
A recombinant subunit vaccine (Shingrix®) was recently licensed for use against herpes zoster. This vaccine is based on glycoprotein E (gE) of varicella zoster virus (VZV), the most abundantly expressed protein of VZV, harboring sites for N- and O-linked glycosylation. The subunit vaccine elicits stronger virus-specific CD4+ T cell response as well as antibody B cell response to gE, compared to the currently used live attenuated vaccine (Zostavax®). This situation is at variance with the current notion since a live vaccine, causing an active virus infection, should be far more efficient than a subunit vaccine based on only one single viral glycoprotein. We previously found gE to be heavily glycosylated, not least by numerous clustered O-linked glycans, when it was produced in human fibroblasts. However, in contrast to Zostavax®, which is produced in fibroblasts, the recombinant gE of Shingrix® is expressed in Chinese hamster ovary (CHO) cells. Hence, the glycan occupancy and glycan structures of gE may differ considerably between the two vaccine types. Here, we aimed at (i) defining the glycan structures and positions of recombinant gE and (ii) identifying possible features of the recombinant gE O-glycosylation pattern contributing to the vaccine efficacy of Shingrix®. Firstly, recombinant gE produced in CHO cells (“Shingrix situation”) is more scarcely decorated by O-linked glycans than gE from human fibroblasts (“Zostavax situation”), with respect to glycan site occupancy. Secondly, screening of immunodominant B cell epitopes of gE, using a synthetic peptide library against serum samples from VZV-seropositive individuals, revealed that the O-linked glycan signature promoted binding of IgG antibodies via a decreased number of interfering O-linked glycans, but also via specific O-linked glycans enhancing antibody binding. These findings may, in part, explain the higher protective efficacy of Shingrix®, and can also be of relevance for development of subunit vaccines to other enveloped viruses. Full article
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17 pages, 4068 KiB  
Article
Specificity of Escherichia coli Heat-Labile Enterotoxin Investigated by Single-Site Mutagenesis and Crystallography
by Julie Elisabeth Heggelund, Joel Benjamin Heim, Gregor Bajc, Vesna Hodnik, Gregor Anderluh and Ute Krengel
Int. J. Mol. Sci. 2019, 20(3), 703; https://doi.org/10.3390/ijms20030703 - 06 Feb 2019
Cited by 7 | Viewed by 4565
Abstract
Diarrhea caused by enterotoxigenic Escherichia coli (ETEC) is one of the leading causes of mortality in children under five years of age and is a great burden on developing countries. The major virulence factor of the bacterium is the heat-labile enterotoxin (LT), a [...] Read more.
Diarrhea caused by enterotoxigenic Escherichia coli (ETEC) is one of the leading causes of mortality in children under five years of age and is a great burden on developing countries. The major virulence factor of the bacterium is the heat-labile enterotoxin (LT), a close homologue of the cholera toxin. The toxins bind to carbohydrate receptors in the gastrointestinal tract, leading to toxin uptake and, ultimately, to severe diarrhea. Previously, LT from human- and porcine-infecting ETEC (hLT and pLT, respectively) were shown to have different carbohydrate-binding specificities, in particular with respect to N-acetyllactosamine-terminating glycosphingolipids. Here, we probed 11 single-residue variants of the heat-labile enterotoxin with surface plasmon resonance spectroscopy and compared the data to the parent toxins. In addition we present a 1.45 Å crystal structure of pLTB in complex with branched lacto-N-neohexaose (Galβ4GlcNAcβ6[Galβ4GlcNAcβ3]Galβ4Glc). The largest difference in binding specificity is caused by mutation of residue 94, which links the primary and secondary binding sites of the toxins. Residue 95 (and to a smaller extent also residues 7 and 18) also contribute, whereas residue 4 shows no effect on monovalent binding of the ligand and may rather be important for multivalent binding and avidity. Full article
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21 pages, 16885 KiB  
Article
Lectin Sequence Distribution in QTLs from Rice (Oryza sativa) Suggest a Role in Morphological Traits and Stress Responses
by Mariya Tsaneva, Kristof De Schutter, Bruno Verstraeten and Els J.M. Van Damme
Int. J. Mol. Sci. 2019, 20(2), 437; https://doi.org/10.3390/ijms20020437 - 20 Jan 2019
Cited by 7 | Viewed by 3732
Abstract
Rice (Oryza sativa) is one of the main staple crops worldwide but suffers from important yield losses due to different abiotic and biotic stresses. Analysis of quantitative trait loci (QTL) is a classical genetic method which enables the creation of more [...] Read more.
Rice (Oryza sativa) is one of the main staple crops worldwide but suffers from important yield losses due to different abiotic and biotic stresses. Analysis of quantitative trait loci (QTL) is a classical genetic method which enables the creation of more resistant cultivars but does not yield information on the genes directly involved or responsible for the desired traits. Lectins are known as proteins with diverse functions in plants. Some of them are abundant proteins in seeds and are considered as storage/defense proteins while other lectins are known as stress-inducible proteins, implicated in stress perception and signal transduction as part of plant innate immunity. We investigated the distribution of lectin sequences in different QTL related to stress tolerance/resistance, morphology, and physiology through mapping of the lectin sequences and QTL regions on the chromosomes and subsequent statistical analysis. Furthermore, the domain structure and evolutionary relationships of the lectins in O. sativa spp. indica and japonica were investigated. Our results revealed that lectin sequences are statistically overrepresented in QTLs for (a)biotic resistance/tolerance as well as in QTLs related to economically important traits such as eating quality and sterility. These findings contribute to the characterization of the QTL sequences and can provide valuable information to the breeders. Full article
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16 pages, 3006 KiB  
Article
Morniga-G, a T/Tn-Specific Lectin, Induces Leukemic Cell Death via Caspase and DR5 Receptor-Dependent Pathways
by Guillaume Poiroux, Annick Barre, Mathias Simplicien, Sandrine Pelofy, Bruno Segui, Els J. M. Van Damme, Pierre Rougé and Hervé Benoist
Int. J. Mol. Sci. 2019, 20(1), 230; https://doi.org/10.3390/ijms20010230 - 08 Jan 2019
Cited by 11 | Viewed by 5853
Abstract
Morniga-G, the Gal-specific black mulberry (Morus nigra) lectin, displays high affinity for T (CD176) and Tn (CD175) antigens, frequently expressed at the cancer cell surface. The effects of Morniga-G were investigated on a Tn-positive leukemic Jurkat cell line. The lectin, used [...] Read more.
Morniga-G, the Gal-specific black mulberry (Morus nigra) lectin, displays high affinity for T (CD176) and Tn (CD175) antigens, frequently expressed at the cancer cell surface. The effects of Morniga-G were investigated on a Tn-positive leukemic Jurkat cell line. The lectin, used in a concentration range between 5–20 μg/mL, induced cell death in leukemic Jurkat cells. Microscopic and cytofluorometric analyses indicated that Jurkat cell death was essentially apoptotic, associated with an increase in the ceramide content and a depolarization of the mitochondrial transmembrane potential. This lectin-mediated cell death was inhibited by the pan caspase-inhibitor zVAD. In addition, cleavage of caspases 8, 9, and 3 was observed in Morniga-G-treated Jurkat cells whereas Jurkat cell lines that are deficient in caspase 8–10, caspase 9, or FADD, survived to the lectin-mediated toxicity. Furthermore, in the presence of TRAIL- or DR5-blocking mononoclonal antibodies, Jurkat cells became resistant to Morniga-G, suggesting that the lectin triggers cell death via the TRAIL/DR5 pathway. In silico computer simulations suggest that Morniga-G might facilitate both the DR5 dimerization and the building of TRAIL/DR5 complexes. Finally, upon treatment of Jurkat cells with benzyl-GalNAc, an O-glycosylation inhibitor, a decrease in Tn antigen expression associating with a reduced Morniga-G toxicity, was observed. Taken together, these results suggest that Morniga-G induces the cell death of Tn-positive leukemic cells via concomitant O-glycosylation-, caspase-, and TRAIL/DR5-dependent pathways. Full article
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Review

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49 pages, 5655 KiB  
Review
Overview of the Structure–Function Relationships of Mannose-Specific Lectins from Plants, Algae and Fungi
by Annick Barre, Yves Bourne, Els J. M. Van Damme and Pierre Rougé
Int. J. Mol. Sci. 2019, 20(2), 254; https://doi.org/10.3390/ijms20020254 - 10 Jan 2019
Cited by 47 | Viewed by 9469
Abstract
To date, a number of mannose-binding lectins have been isolated and characterized from plants and fungi. These proteins are composed of different structural scaffold structures which harbor a single or multiple carbohydrate-binding sites involved in the specific recognition of mannose-containing glycans. Generally, the [...] Read more.
To date, a number of mannose-binding lectins have been isolated and characterized from plants and fungi. These proteins are composed of different structural scaffold structures which harbor a single or multiple carbohydrate-binding sites involved in the specific recognition of mannose-containing glycans. Generally, the mannose-binding site consists of a small, central, carbohydrate-binding pocket responsible for the “broad sugar-binding specificity” toward a single mannose molecule, surrounded by a more extended binding area responsible for the specific recognition of larger mannose-containing N-glycan chains. Accordingly, the mannose-binding specificity of the so-called mannose-binding lectins towards complex mannose-containing N-glycans depends largely on the topography of their mannose-binding site(s). This structure–function relationship introduces a high degree of specificity in the apparently homogeneous group of mannose-binding lectins, with respect to the specific recognition of high-mannose and complex N-glycans. Because of the high specificity towards mannose these lectins are valuable tools for deciphering and characterizing the complex mannose-containing glycans that decorate both normal and transformed cells, e.g., the altered high-mannose N-glycans that often occur at the surface of various cancer cells. Full article
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24 pages, 3937 KiB  
Review
ConA-Like Lectins: High Similarity Proteins as Models to Study Structure/Biological Activities Relationships
by Benildo S. Cavada, Vanir R. Pinto-Junior, Vinicius J. S. Osterne and Kyria S. Nascimento
Int. J. Mol. Sci. 2019, 20(1), 30; https://doi.org/10.3390/ijms20010030 - 21 Dec 2018
Cited by 44 | Viewed by 5478
Abstract
Lectins are a widely studied group of proteins capable of specific and reversible binding to carbohydrates. Undoubtedly, the best characterized are those extracted from plants of the Leguminosae family. Inside this group of proteins, those from the Diocleinae subtribe have attracted attention, in [...] Read more.
Lectins are a widely studied group of proteins capable of specific and reversible binding to carbohydrates. Undoubtedly, the best characterized are those extracted from plants of the Leguminosae family. Inside this group of proteins, those from the Diocleinae subtribe have attracted attention, in particular Concanavalin A (ConA), the best-studied lectin of the group. Diocleinae lectins, also called ConA-like lectins, present a high similarity of sequence and three-dimensional structure and are known to present inflammatory, vasoactive, antibiotic, immunomodulatory and antitumor activities, among others. This high similarity of lectins inside the ConA-like group makes it possible to use them to study structure/biological activity relationships by the variability of both carbohydrate specificity and biological activities results. It is in this context the following review aims to summarize the most recent data on the biochemical and structural properties, as well as biological activities, of ConA-like lectins and the use of these lectins as models to study structure/biological activity relationships. Full article
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