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Special Issue "Protein-Carbohydrate Interactions, and Beyond"

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A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Metabolites".

Deadline for manuscript submissions: closed (15 March 2015)

Special Issue Editors

Guest Editor
Prof. Dr. Els Van Damme (Website)

Ghent University, Belgium
Interests: lectins; carbohydrate-binding proteins; protein-carbohydrate interactions; carbohydrate recognition; glycosylation; biological activity; ribosome inactivating proteins; toxin domain; physiological importance; defense and immunity; stress proteins; glycobiology
Guest Editor
Dr. Kristof De Schutter

Ghent University, Belgium
Interests: lectins; carbohydrate-binding proteins; protein-carbohydrate interactions; carbohydrate recognition; glycosylation; glycosylation engineering; cellular localization; cell biological function; stress response; pharmaceutical protein production; yeast engineering, cell cycle; DNA stress; genomics

Special Issue Information

Dear Colleagues,

This special issue of Molecules is dedicated to Protein-Carbohydrate Interactions. In recent years, it has been clearly established that protein-carbohydrate interactions underlie many important biological events. Carbohydrate chains of glycoproteins, glycolipids, proteoglycans, and polysaccharides mediate a multitude of biological processes through their interactions with carbohydrate-recognizing and binding proteins. The importance of protein carbohydrate recognition has been validated with the consolidation of the field of glycobiology.

In animal systems, numerous regulatory programs have been deciphered, demonstrating that carbohydrate-binding proteins contribute to cellular signalling through interaction with specific N- and O-glycans present on their interacting partners. Although much less information is available with respect to the importance of protein-carbohydrate recognition in other kingdoms of life, these interactions are clearly of the utmost importance for defence reactions, stress signalling, growth, and development. The specific recognition between a protein and a carbohydrate is often only a first step in a sequence of events. This Special Issue will concentrate on protein-carbohydrate interactions and their biological significance. We encourage authors to submit research papers and comprehensive reviews for this Special Issue, and hope that the topics covered will enlighten the fascinating world of glycobiology.

Prof. Dr. Els Van Damme
Dr. Kristof De Schutter
Guest Editors

Prof. Dr. Els Van Damme Dr. Kristof De Schutter

Submission

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. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as 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 refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed Open Access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs).


Published Papers (18 papers)

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Editorial

Jump to: Research, Review

Open AccessEditorial Protein-Carbohydrate Interactions, and Beyond …
Molecules 2015, 20(8), 15202-15205; doi:10.3390/molecules200815202
Received: 17 August 2015 / Revised: 17 August 2015 / Accepted: 19 August 2015 / Published: 20 August 2015
PDF Full-text (630 KB) | HTML Full-text | XML Full-text
Abstract Carbohydrates are ubiquitous and play an intriguing role inside the cell as well as on the cell surface.[...] Full article
(This article belongs to the Special Issue Protein-Carbohydrate Interactions, and Beyond)

Research

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Open AccessArticle Molecular Cloning, Carbohydrate Specificity and the Crystal Structure of Two Sclerotium rolfsii Lectin Variants
Molecules 2015, 20(6), 10848-10865; doi:10.3390/molecules200610848
Received: 31 March 2015 / Revised: 3 June 2015 / Accepted: 5 June 2015 / Published: 12 June 2015
Cited by 2 | PDF Full-text (2259 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
SRL is a cell wall associated developmental-stage specific lectin secreted by Sclerotium rolfsii, a soil-born pathogenic fungus. SRL displays specificity for TF antigen (Galβ1→3GalNAc-α-Ser//Thr) expressed in all cancer types and has tumour suppressing effects in vivo. Considering the immense potential [...] Read more.
SRL is a cell wall associated developmental-stage specific lectin secreted by Sclerotium rolfsii, a soil-born pathogenic fungus. SRL displays specificity for TF antigen (Galβ1→3GalNAc-α-Ser//Thr) expressed in all cancer types and has tumour suppressing effects in vivo. Considering the immense potential of SRL in cancer research, we have generated two variant gene constructs of SRL and expressed in E. coli to refine the sugar specificity and solubility by altering the surface charge. SSR1 and SSR2 are two different recombinant variants of SRL, both of which recognize TF antigen but only SSR1 binds to Tn antigen (GalNAcα-Ser/Thr). The glycan array analysis of the variants demonstrated that SSR1 recognizes TF antigen and their derivative with high affinity similar to SRL but showed highest affinity towards the sialylated Tn antigen, unlike SRL. The carbohydrate binding property of SSR2 remains unaltered compared to SRL. The crystal structures of the two variants were determined in free form and in complex with N-acetylglucosamine at 1.7 Å and 1.6 Å resolution, respectively. Structural analysis highlighted the structural basis of the fine carbohydrate specificity of the two SRL variants and results are in agreement with glycan array analysis. Full article
(This article belongs to the Special Issue Protein-Carbohydrate Interactions, and Beyond)
Figures

Open AccessArticle Molecular Characterisation of the Haemagglutinin Glycan-Binding Specificity of Egg-Adapted Vaccine Strains of the Pandemic 2009 H1N1 Swine Influenza A Virus
Molecules 2015, 20(6), 10415-10434; doi:10.3390/molecules200610415
Received: 13 May 2015 / Accepted: 1 June 2015 / Published: 5 June 2015
Cited by 2 | PDF Full-text (3553 KB) | HTML Full-text | XML Full-text
Abstract
The haemagglutinin (HA) glycan binding selectivity of H1N1 influenza viruses is an important determinant for the host range of the virus and egg-adaption during vaccine production. This study integrates glycan binding data with structure-recognition models to examine the impact of the K123N, [...] Read more.
The haemagglutinin (HA) glycan binding selectivity of H1N1 influenza viruses is an important determinant for the host range of the virus and egg-adaption during vaccine production. This study integrates glycan binding data with structure-recognition models to examine the impact of the K123N, D225G and Q226R mutations (as seen in the HA of vaccine strains of the pandemic 2009 H1N1 swine influenza A virus). The glycan-binding selectivity of three A/California/07/09 vaccine production strains, and purified recombinant A/California/07/09 HAs harboring these mutations was examined via a solid-phase ELISA assay. Wild-type A/California/07/09 recombinant HA bound specifically to α2,6-linked sialyl-glycans, with no affinity for the α2,3-linked sialyl-glycans in the array. In contrast, the vaccine virus strains and recombinant HA harboring the Q226R HA mutation displayed a comparable pattern of highly specific binding to α2,3-linked sialyl-glycans, with a negligible affinity for α2,6-linked sialyl-glycans. The D225G A/California/07/09 recombinant HA displayed an enhanced binding affinity for both α2,6- and α2,3-linked sialyl-glycans in the array. Notably its α2,6-glycan affinity was generally higher compared to its α2,3-glycan affinity, which may explain why the double mutant was not naturally selected during egg-adaption of the virus. The K123N mutation which introduces a glycosylation site proximal to the receptor binding site, did not impact the α2,3/α2,6 glycan selectivity, however, it lowered the overall glycan binding affinity of the HA; suggesting glycosylation may interfere with receptor binding. Docking models and ‘per residues’ scoring were employed to provide a structure-recognition rational for the experimental glycan binding data. Collectively, the glycan binding data inform future vaccine design strategies to introduce the D225G or Q226R amino acid substitutions into recombinant H1N1 viruses. Full article
(This article belongs to the Special Issue Protein-Carbohydrate Interactions, and Beyond)
Open AccessArticle Effect of Chum Salmon Egg Lectin on Tight Junctions in Caco-2 Cell Monolayers
Molecules 2015, 20(5), 8094-8106; doi:10.3390/molecules20058094
Received: 8 March 2015 / Revised: 20 April 2015 / Accepted: 30 April 2015 / Published: 5 May 2015
Cited by 3 | PDF Full-text (1473 KB) | HTML Full-text | XML Full-text
Abstract
The effect of a chum salmon egg lectin (CSL3) on tight junction (TJ) of Caco-2 cell monolayers was investigated. The lectin opened TJ as indicated by the decrease of the transepithelial electrical resistance (TER) value and the increase of the permeation of [...] Read more.
The effect of a chum salmon egg lectin (CSL3) on tight junction (TJ) of Caco-2 cell monolayers was investigated. The lectin opened TJ as indicated by the decrease of the transepithelial electrical resistance (TER) value and the increase of the permeation of lucifer yellow, which is transported via the TJ-mediated paracellular pathway. The effects of CSL3 were inhibited by the addition of 10 mM L-rhamnose or D-galactose which were specific sugars for CSL3. The lectin increased the intracellular Ca2+ of Caco-2 cell monolayers, that could be inhibited by the addition of L-rhamnose. The fluorescence immunostaining of β-actin in Caco-2 cell monolayers revealed that the cytoskeleton was changed by the CSL3 treatment, suggesting that CSL3 depolymerized β-actin to cause reversible TJ structural and functional disruption. Although Japanese jack bean lectin and wheat germ lectin showed similar effects in the decrease of the TER values and the increase of the intracellular Ca2+, they could not be inhibited by the same concentrations of simple sugars, such as D-glucose and N-acetyl-D-glucosamine. Full article
(This article belongs to the Special Issue Protein-Carbohydrate Interactions, and Beyond)
Open AccessArticle Proteomic Analysis of Polysaccharide-Milk Protein Interactions Induced by Chitosan
Molecules 2015, 20(5), 7737-7749; doi:10.3390/molecules20057737
Received: 6 March 2015 / Revised: 19 April 2015 / Accepted: 23 April 2015 / Published: 28 April 2015
Cited by 3 | PDF Full-text (6803 KB) | HTML Full-text | XML Full-text
Abstract
The chitosan-induced coacervation of milk proteins was investigated using a proteomic approach. The addition of 0.8% chitosan to milk caused the milk proteins to coacervate after a 1 h incubation period. Approximately 86% of the milk proteins were present in the milk [...] Read more.
The chitosan-induced coacervation of milk proteins was investigated using a proteomic approach. The addition of 0.8% chitosan to milk caused the milk proteins to coacervate after a 1 h incubation period. Approximately 86% of the milk proteins were present in the milk pellet fraction (MPF), and the protein concentration of the milk supernatant fraction (MSF) decreased from 29.4 ± 0.2 to 4.2 ± 0.6 mg/mL. SDS-PAGE analysis showed that the total intensities of serum albumin (BSA), αS-casein (αS-CN), β-casein (β-CN), κ-casein (κ-CN) and β-lactoglobulin (β-LG) in the MSF decreased to 8.5% ± 0.2%, 0.9% ± 0.3%, 0.7% ± 0.3%, 0.5% ± 0.2% and 15.0% ± 0.5%, respectively. Two-dimensional electrophoresis analysis indicated that αS1-, αS2-, β- and κ-CN and a fraction of the β-LG and BSA were found in the MSF following incubation with 0.8% chitosan. Isothermal titration calorimetry analysis indicated that binding of chitosan to milk proteins is an exothermic reaction based on binding titration curves of milk proteins dispersions with chitosan, and the enthalpy of binding (ΔH) and binding constant (Ka) were −7.85 × 104 cal/mol and 1.06 × 105/mol, respectively. These results suggested that the addition of 0.8% chitosan causes milk proteins to coacervate due to polysaccharide-protein interactions. Full article
(This article belongs to the Special Issue Protein-Carbohydrate Interactions, and Beyond)
Open AccessArticle Glycodendrimers and Modified ELISAs: Tools to Elucidate Multivalent Interactions of Galectins 1 and 3
Molecules 2015, 20(4), 7059-7096; doi:10.3390/molecules20047059
Received: 5 March 2015 / Revised: 29 March 2015 / Accepted: 1 April 2015 / Published: 20 April 2015
Cited by 2 | PDF Full-text (2718 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Multivalent protein-carbohydrate interactions that are mediated by sugar-binding proteins, i.e., lectins, have been implicated in a myriad of intercellular recognition processes associated with tumor progression such as galectin-mediated cancer cellular migration/metastatic processes. Here, using a modified ELISA, we show that glycodendrimers [...] Read more.
Multivalent protein-carbohydrate interactions that are mediated by sugar-binding proteins, i.e., lectins, have been implicated in a myriad of intercellular recognition processes associated with tumor progression such as galectin-mediated cancer cellular migration/metastatic processes. Here, using a modified ELISA, we show that glycodendrimers bearing mixtures of galactosides, lactosides, and N-acetylgalactosaminosides, galectin-3 ligands, multivalently affect galectin-3 functions. We further demonstrate that lactose functionalized glycodendrimers multivalently bind a different member of the galectin family, i.e., galectin-1. In a modified ELISA, galectin-3 recruitment by glycodendrimers was shown to directly depend on the ratio of low to high affinity ligands on the dendrimers, with lactose-functionalized dendrimers having the highest activity and also binding well to galectin-1. The results depicted here indicate that synthetic multivalent systems and upfront assay formats will improve the understanding of the multivalent function of galectins during multivalent protein carbohydrate recognition/interaction. Full article
(This article belongs to the Special Issue Protein-Carbohydrate Interactions, and Beyond)
Open AccessArticle Mouse Mincle: Characterization as a Model for Human Mincle and Evolutionary Implications
Molecules 2015, 20(4), 6670-6682; doi:10.3390/molecules20046670
Received: 13 March 2015 / Revised: 7 April 2015 / Accepted: 13 April 2015 / Published: 15 April 2015
Cited by 3 | PDF Full-text (2652 KB) | HTML Full-text | XML Full-text
Abstract
Mincle, the macrophage-inducible C-type lectin also known as CLEC-4E, binds to the mycobacterial glycolipid trehalose dimycolate and initiates a signaling cascade by serving as a receptor for Mycobacterium tuberculosis and other pathogenic mycobacterial species. Studies of the biological functions of human mincle [...] Read more.
Mincle, the macrophage-inducible C-type lectin also known as CLEC-4E, binds to the mycobacterial glycolipid trehalose dimycolate and initiates a signaling cascade by serving as a receptor for Mycobacterium tuberculosis and other pathogenic mycobacterial species. Studies of the biological functions of human mincle often rely on mouse models, based on the assumption that the biological properties of the mouse receptor mimic those of the human protein. Experimental support for this assumption has been obtained by expression of the carbohydrate-recognition domain of mouse mincle and characterization of its interaction with small molecule analogs of trehalose dimycolate. The results confirm that the ligand-binding properties of mouse mincle closely parallel those of the human receptor. These findings are consistent with the conservation of key amino acid residues that have been shown to form the ligand-binding site in human and cow mincle. Sequence alignment reveals that these residues are conserved in a wide range of mammalian species, suggesting that mincle has a conserved function in binding ligands that may include endogenous mammalian glycans or pathogen glycans in addition to trehalose dimycolate. Full article
(This article belongs to the Special Issue Protein-Carbohydrate Interactions, and Beyond)

Review

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Open AccessReview Glycoprotein Quality Control and Endoplasmic Reticulum Stress
Molecules 2015, 20(8), 13689-13704; doi:10.3390/molecules200813689
Received: 27 April 2015 / Revised: 22 July 2015 / Accepted: 24 July 2015 / Published: 28 July 2015
Cited by 6 | PDF Full-text (1101 KB) | HTML Full-text | XML Full-text
Abstract
The endoplasmic reticulum (ER) supports many cellular processes and performs diverse functions, including protein synthesis, translocation across the membrane, integration into the membrane, folding, and posttranslational modifications including N-linked glycosylation; and regulation of Ca2+ homeostasis. In mammalian systems, the majority [...] Read more.
The endoplasmic reticulum (ER) supports many cellular processes and performs diverse functions, including protein synthesis, translocation across the membrane, integration into the membrane, folding, and posttranslational modifications including N-linked glycosylation; and regulation of Ca2+ homeostasis. In mammalian systems, the majority of proteins synthesized by the rough ER have N-linked glycans critical for protein maturation. The N-linked glycan is used as a quality control signal in the secretory protein pathway. A series of chaperones, folding enzymes, glucosidases, and carbohydrate transferases support glycoprotein synthesis and processing. Perturbation of ER-associated functions such as disturbed ER glycoprotein quality control, protein glycosylation and protein folding results in activation of an ER stress coping response. Collectively this ER stress coping response is termed the unfolded protein response (UPR), and occurs through the activation of complex cytoplasmic and nuclear signaling pathways. Cellular and ER homeostasis depends on balanced activity of the ER protein folding, quality control, and degradation pathways; as well as management of the ER stress coping response. Full article
(This article belongs to the Special Issue Protein-Carbohydrate Interactions, and Beyond)
Open AccessReview Mucin-Type O-Glycosylation in Invertebrates
Molecules 2015, 20(6), 10622-10640; doi:10.3390/molecules200610622
Received: 14 March 2015 / Revised: 1 June 2015 / Accepted: 3 June 2015 / Published: 9 June 2015
Cited by 1 | PDF Full-text (892 KB) | HTML Full-text | XML Full-text
Abstract
O-Glycosylation is one of the most important posttranslational modifications of proteins. It takes part in protein conformation, protein sorting, developmental processes and the modulation of enzymatic activities. In vertebrates, the basics of the biosynthetic pathway of O-glycans are already well [...] Read more.
O-Glycosylation is one of the most important posttranslational modifications of proteins. It takes part in protein conformation, protein sorting, developmental processes and the modulation of enzymatic activities. In vertebrates, the basics of the biosynthetic pathway of O-glycans are already well understood. However, the regulation of the processes and the molecular aspects of defects, especially in correlation with cancer or developmental abnormalities, are still under investigation. The knowledge of the correlating invertebrate systems and evolutionary aspects of these highly conserved biosynthetic events may help improve the understanding of the regulatory factors of this pathway. Invertebrates display a broad spectrum of glycosylation varieties, providing an enormous potential for glycan modifications which may be used for the design of new pharmaceutically active substances. Here, overviews of the present knowledge of invertebrate mucin-type O-glycan structures and the currently identified enzymes responsible for the biosynthesis of these oligosaccharides are presented, and the few data dealing with functional aspects of O-glycans are summarised. Full article
(This article belongs to the Special Issue Protein-Carbohydrate Interactions, and Beyond)
Open AccessReview Molecular Interactions of β-(1→3)-Glucans with Their Receptors
Molecules 2015, 20(6), 9745-9766; doi:10.3390/molecules20069745
Received: 14 April 2015 / Accepted: 20 May 2015 / Published: 27 May 2015
Cited by 6 | PDF Full-text (1539 KB) | HTML Full-text | XML Full-text
Abstract
β-(1→3)-Glucans can be found as structural polysaccharides in cereals, in algae or as exo-polysaccharides secreted on the surfaces of mushrooms or fungi. Research has now established that β-(1→3)-glucans can trigger different immune responses and act as efficient immunostimulating agents. They constitute prevalent [...] Read more.
β-(1→3)-Glucans can be found as structural polysaccharides in cereals, in algae or as exo-polysaccharides secreted on the surfaces of mushrooms or fungi. Research has now established that β-(1→3)-glucans can trigger different immune responses and act as efficient immunostimulating agents. They constitute prevalent sources of carbons for microorganisms after subsequent recognition by digesting enzymes. Nevertheless, mechanisms associated with both roles are not yet clearly understood. This review focuses on the variety of elucidated molecular interactions that involve these natural or synthetic polysaccharides and their receptors, i.e., Dectin-1, CR3, glycolipids, langerin and carbohydrate-binding modules. Full article
(This article belongs to the Special Issue Protein-Carbohydrate Interactions, and Beyond)
Figures

Open AccessReview The Role of Lectin-Carbohydrate Interactions in the Regulation of ER-Associated Protein Degradation
Molecules 2015, 20(6), 9816-9846; doi:10.3390/molecules20069816
Received: 28 April 2015 / Revised: 20 May 2015 / Accepted: 21 May 2015 / Published: 27 May 2015
Cited by 2 | PDF Full-text (1353 KB) | HTML Full-text | XML Full-text
Abstract
Proteins entering the secretory pathway are translocated across the endoplasmic reticulum (ER) membrane in an unfolded form. In the ER they are restricted to a quality control system that ensures correct folding or eventual degradation of improperly folded polypeptides. Mannose trimming of [...] Read more.
Proteins entering the secretory pathway are translocated across the endoplasmic reticulum (ER) membrane in an unfolded form. In the ER they are restricted to a quality control system that ensures correct folding or eventual degradation of improperly folded polypeptides. Mannose trimming of N-glycans on newly synthesized proteins plays an important role in the recognition and sorting of terminally misfolded glycoproteins for ER-associated protein degradation (ERAD). In this process misfolded proteins are retrotranslocated into the cytosol, polyubiquitinated, and eventually degraded by the proteasome. The mechanism by which misfolded glycoproteins are recognized and recruited to the degradation machinery has been extensively studied during last decade. In this review, we focus on ER degradation-enhancing α-mannosidase-like protein (EDEM) family proteins that seem to play a key role in the discrimination between proteins undergoing a folding process and terminally misfolded proteins directed for degradation. We describe interactions of EDEM proteins with other components of the ERAD machinery, as well as with various protein substrates. Carbohydrate-dependent interactions together with N-glycan-independent interactions seem to regulate the complex process of protein recognition and direction for proteosomal degradation. Full article
(This article belongs to the Special Issue Protein-Carbohydrate Interactions, and Beyond)
Figures

Open AccessReview Protein-Carbohydrate Interaction between Sperm and the Egg-Coating Envelope and Its Regulation by Dicalcin, a Xenopus laevis Zona Pellucida Protein-Associated Protein
Molecules 2015, 20(5), 9468-9486; doi:10.3390/molecules20059468
Received: 3 March 2015 / Accepted: 13 May 2015 / Published: 22 May 2015
Cited by 1 | PDF Full-text (936 KB) | HTML Full-text | XML Full-text
Abstract
Protein-carbohydrate interaction regulates multiple important processes during fertilization, an essential biological event where individual gametes undergo intercellular recognition to fuse and generate a zygote. In the mammalian female reproductive tract, sperm temporarily adhere to the oviductal epithelium via the complementary interaction between [...] Read more.
Protein-carbohydrate interaction regulates multiple important processes during fertilization, an essential biological event where individual gametes undergo intercellular recognition to fuse and generate a zygote. In the mammalian female reproductive tract, sperm temporarily adhere to the oviductal epithelium via the complementary interaction between carbohydrate-binding proteins on the sperm membrane and carbohydrates on the oviductal cells. After detachment from the oviductal epithelium at the appropriate time point following ovulation, sperm migrate and occasionally bind to the extracellular matrix, called the zona pellucida (ZP), which surrounds the egg, thereafter undergoing the exocytotic acrosomal reaction to penetrate the envelope and to reach the egg plasma membrane. This sperm-ZP interaction also involves the direct interaction between sperm carbohydrate-binding proteins and carbohydrates within the ZP, most of which have been conserved across divergent species from mammals to amphibians and echinoderms. This review focuses on the carbohydrate-mediated interaction of sperm with the female reproductive tract, mainly the interaction between sperm and the ZP, and introduces the fertilization-suppressive action of dicalcin, a Xenopus laevis ZP protein-associated protein. The action of dicalcin correlates significantly with a dicalcin-dependent change in the lectin-staining pattern within the ZP, suggesting a unique role of dicalcin as an inherent protein that is capable of regulating the affinity between the lectin and oligosaccharides attached on its target glycoprotein. Full article
(This article belongs to the Special Issue Protein-Carbohydrate Interactions, and Beyond)
Open AccessReview Protein-Carbohydrate Interactions as Part of Plant Defense and Animal Immunity
Molecules 2015, 20(5), 9029-9053; doi:10.3390/molecules20059029
Received: 7 April 2015 / Revised: 12 May 2015 / Accepted: 14 May 2015 / Published: 19 May 2015
Cited by 9 | PDF Full-text (2985 KB) | HTML Full-text | XML Full-text
Abstract
The immune system consists of a complex network of cells and molecules that interact with each other to initiate the host defense system. Many of these interactions involve specific carbohydrate structures and proteins that specifically recognize and bind them, in particular lectins. [...] Read more.
The immune system consists of a complex network of cells and molecules that interact with each other to initiate the host defense system. Many of these interactions involve specific carbohydrate structures and proteins that specifically recognize and bind them, in particular lectins. It is well established that lectin-carbohydrate interactions play a major role in the immune system, in that they mediate and regulate several interactions that are part of the immune response. Despite obvious differences between the immune system in animals and plants, there are also striking similarities. In both cases, lectins can play a role as pattern recognition receptors, recognizing the pathogens and initiating the stress response. Although plants do not possess an adaptive immune system, they are able to imprint a stress memory, a mechanism in which lectins can be involved. This review will focus on the role of lectins in the immune system of animals and plants. Full article
(This article belongs to the Special Issue Protein-Carbohydrate Interactions, and Beyond)
Figures

Open AccessReview Hitting the Sweet Spot: Glycans as Targets of Fungal Defense Effector Proteins
Molecules 2015, 20(5), 8144-8167; doi:10.3390/molecules20058144
Received: 2 April 2015 / Revised: 29 April 2015 / Accepted: 30 April 2015 / Published: 6 May 2015
Cited by 4 | PDF Full-text (1049 KB) | HTML Full-text | XML Full-text
Abstract
Organisms which rely solely on innate defense systems must combat a large number of antagonists with a comparatively low number of defense effector molecules. As one solution of this problem, these organisms have evolved effector molecules targeting epitopes that are conserved between [...] Read more.
Organisms which rely solely on innate defense systems must combat a large number of antagonists with a comparatively low number of defense effector molecules. As one solution of this problem, these organisms have evolved effector molecules targeting epitopes that are conserved between different antagonists of a specific taxon or, if possible, even of different taxa. In order to restrict the activity of the defense effector molecules to physiologically relevant taxa, these target epitopes should, on the other hand, be taxon-specific and easily accessible. Glycans fulfill all these requirements and are therefore a preferred target of defense effector molecules, in particular defense proteins. Here, we review this defense strategy using the example of the defense system of multicellular (filamentous) fungi against microbial competitors and animal predators. Full article
(This article belongs to the Special Issue Protein-Carbohydrate Interactions, and Beyond)
Open AccessReview Investigation of Carbohydrate Recognition via Computer Simulation
Molecules 2015, 20(5), 7700-7718; doi:10.3390/molecules20057700
Received: 12 March 2015 / Revised: 15 April 2015 / Accepted: 15 April 2015 / Published: 28 April 2015
Cited by 6 | PDF Full-text (1087 KB) | HTML Full-text | XML Full-text
Abstract
Carbohydrate recognition by proteins, such as lectins and other (bio)molecules, can be essential for many biological functions. Recently, interest has arisen due to potential protein and drug design and future bioengineering applications. A quantitative measurement of carbohydrate-protein interaction is thus important for [...] Read more.
Carbohydrate recognition by proteins, such as lectins and other (bio)molecules, can be essential for many biological functions. Recently, interest has arisen due to potential protein and drug design and future bioengineering applications. A quantitative measurement of carbohydrate-protein interaction is thus important for the full characterization of sugar recognition. We focus on the aspect of utilizing computer simulations and biophysical models to evaluate the strength and specificity of carbohydrate recognition in this review. With increasing computational resources, better algorithms and refined modeling parameters, using state-of-the-art supercomputers to calculate the strength of the interaction between molecules has become increasingly mainstream. We review the current state of this technique and its successful applications for studying protein-sugar interactions in recent years. Full article
(This article belongs to the Special Issue Protein-Carbohydrate Interactions, and Beyond)
Open AccessReview Lectin Engineering, a Molecular Evolutionary Approach to Expanding the Lectin Utilities
Molecules 2015, 20(5), 7637-7656; doi:10.3390/molecules20057637
Received: 31 March 2015 / Revised: 20 April 2015 / Accepted: 20 April 2015 / Published: 27 April 2015
Cited by 2 | PDF Full-text (1130 KB) | HTML Full-text | XML Full-text
Abstract
In the post genomic era, glycomics—the systematic study of all glycan structures of a given cell or organism—has emerged as an indispensable technology in various fields of biology and medicine. Lectins are regarded as “decipherers of glycans”, being useful reagents for their [...] Read more.
In the post genomic era, glycomics—the systematic study of all glycan structures of a given cell or organism—has emerged as an indispensable technology in various fields of biology and medicine. Lectins are regarded as “decipherers of glycans”, being useful reagents for their structural analysis, and have been widely used in glycomic studies. However, the inconsistent activity and availability associated with the plant-derived lectins that comprise most of the commercially available lectins, and the limit in the range of glycan structures covered, have necessitated the development of innovative tools via engineering of lectins on existing scaffolds. This review will summarize the current state of the art of lectin engineering and highlight recent technological advances in this field. The key issues associated with the strategy of lectin engineering including selection of template lectin, construction of a mutagenesis library, and high-throughput screening methods are discussed. Full article
(This article belongs to the Special Issue Protein-Carbohydrate Interactions, and Beyond)
Open AccessReview Heparin/Heparan Sulfate Proteoglycans Glycomic Interactome in Angiogenesis: Biological Implications and Therapeutical Use
Molecules 2015, 20(4), 6342-6388; doi:10.3390/molecules20046342
Received: 26 February 2015 / Revised: 31 March 2015 / Accepted: 1 April 2015 / Published: 10 April 2015
Cited by 10 | PDF Full-text (1610 KB) | HTML Full-text | XML Full-text
Abstract
Angiogenesis, the process of formation of new blood vessel from pre-existing ones, is involved in various intertwined pathological processes including virus infection, inflammation and oncogenesis, making it a promising target for the development of novel strategies for various interventions. To induce angiogenesis, [...] Read more.
Angiogenesis, the process of formation of new blood vessel from pre-existing ones, is involved in various intertwined pathological processes including virus infection, inflammation and oncogenesis, making it a promising target for the development of novel strategies for various interventions. To induce angiogenesis, angiogenic growth factors (AGFs) must interact with pro-angiogenic receptors to induce proliferation, protease production and migration of endothelial cells (ECs). The action of AGFs is counteracted by antiangiogenic modulators whose main mechanism of action is to bind (thus sequestering or masking) AGFs or their receptors. Many sugars, either free or associated to proteins, are involved in these interactions, thus exerting a tight regulation of the neovascularization process. Heparin and heparan sulfate proteoglycans undoubtedly play a pivotal role in this context since they bind to almost all the known AGFs, to several pro-angiogenic receptors and even to angiogenic inhibitors, originating an intricate network of interaction, the so called “angiogenesis glycomic interactome”. The decoding of the angiogenesis glycomic interactome, achievable by a systematic study of the interactions occurring among angiogenic modulators and sugars, may help to design novel antiangiogenic therapies with implications in the cure of angiogenesis-dependent diseases. Full article
(This article belongs to the Special Issue Protein-Carbohydrate Interactions, and Beyond)
Open AccessReview HIV-1 and Its Resistance to Peptidic Carbohydrate-Binding Agents (CBAs): An Overview
Molecules 2014, 19(12), 21085-21112; doi:10.3390/molecules191221085
Received: 22 October 2014 / Revised: 4 December 2014 / Accepted: 8 December 2014 / Published: 15 December 2014
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Abstract
The glycoproteins on the surfaces of enveloped viruses, such as HIV, can be considered as a unique target for antiviral therapy. Different carbohydrate-binding agents (CBAs) target specific glycans present on viral glycoproteins of enveloped viruses. It has been shown that long-term CBA [...] Read more.
The glycoproteins on the surfaces of enveloped viruses, such as HIV, can be considered as a unique target for antiviral therapy. Different carbohydrate-binding agents (CBAs) target specific glycans present on viral glycoproteins of enveloped viruses. It has been shown that long-term CBA pressure in vitro can result in mutant HIV-1 isolates with several N-linked glycan deletions on gp120. These studies demonstrated that mainly high-mannose type glycans are deleted. However, interestingly, N241, N262 and N356 on gp120 have never been found to be affected after prolonged CBA exposure. Here, we review the mutation and (cross)-resistance profiles of eleven specific generated CBA-resistant HIV-1 strains. We observed that the broad-neutralizing anti-carbohydrate binding mAb 2G12 became completely inactive against all the generated CBA-resistant HIV-1 clade B isolates. In addition, all of the CBAs discussed in this review, with the exception of NICTABA, interfered with the binding of 2G12 mAb to gp120 expressed on HIV-1-infected T cells. The cross-resistance profiles of mutant HIV-1 strains are varying from increased susceptibility to very high resistance levels, even among different classes of CBAs with dissimilar sugar specificities or binding moieties [e.g., α(1,3), α(1,2), α(1,6)]. Recent studies demonstrated promising results in non-topical formulations (e.g., intranasally or subcutaneously), highlighting their potential for prevention (microbicides) and antiviral therapy. Full article
(This article belongs to the Special Issue Protein-Carbohydrate Interactions, and Beyond)

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