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1. Regulation of mucosal lectins in the oyster Crassostrea virginica in response to food availability and environmental factors

   https://doi.org/10.1093/mollus/eyaa037  

   Allam, Simon; Allam, Bassem; Pales Espinosa, Emmanuelle (February 2021, Journal of Molluscan Studies)

   null (Ed.)

   ABSTRACT Lectins are a large and diverse group of sugar-binding proteins involved in nonself recognition and cell-to-cell interactions. Suspension-feeding bivalves, such as the oyster Crassostrea virginica, are capable of using these molecules to bind cell surface carbohydrates of food particles, allowing particle capture and selection. The aim of this project was to assess whether the expression of mucosal lectins in C. virginica is constant or changes with the season, and to determine whether lectin expression is linked to environmental parameters and/or internal biological factors (gametogenesis). A total of 130 oysters were placed in submerged cages at a tidal estuary and monitored for changes in lectin gene expression over a 1-year period. In parallel, environmental parameters prevailing at the field site, including seawater physicochemical characteristics (temperature, salinity and dissolved oxygen), particulate organic matter and chlorophyll contents, were also monitored. Throughout the study, oysters were dissected and the gills were collected and used for the assessment of the expression of three different lectin genes (CvML, CvML3914 and CvML3912). Remaining tissues were processed for histology and the classification of the gonad development stage. Results showed that when food is abundant, such as during the spring bloom, lectin gene expressions are low, and inversely lectin levels increase with lower food levels. These findings suggest that oysters increase lectin expression to enhance the capture and ingestion of scarce food, while during spring, enough food is already being ingested and lectins are not needed. Furthermore, results showed that as the energy demands of oysters increase (gonad maturation), lectin gene expressions also increase to enhance selective ingestion of nutritious food particles. This study, therefore, demonstrates the seasonality of lectin gene expression in C. virginica, and suggests that lectin regulation is related to the reproduction process and abundance of high-quality food. 

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2. Tailoring Metallosupramolecular Glycoassemblies for Enhancing Lectin Recognition

   https://doi.org/10.1002/anie.202408751  

   Stauber, Julia M (October 2024, Angewandte Chemie International Edition)

   Abstract Multivalency is a fundamental principle in nature that leads to high‐affinity intermolecular recognition through multiple cooperative interactions that overcome the weak binding of individual constituents. For example, multivalency plays a critical role in lectin‐carbohydrate interactions that participate in many essential biological processes. Designing high‐affinity multivalent glycoconjugates that engage lectins results in systems with the potential to disrupt these biological processes, offering promising applications in therapeutic design and bioengineering. Here, a versatile and tunable synthetic platform for the synthesis of metallosupramolecular glycoassemblies is presented that leverages subcomponent self‐assembly, which employs metal ion templates to generate complex supramolecular architectures from simple precursors in one pot. Through ligand design, this approach provides precise control over molecular parameters such as size, shape, flexibility, valency, and charge, which afforded a diverse family of well‐defined hybrid glyconanoassemblies. Evaluation of these complexes as multivalent binders to Concanavalin A (Con A) by isothermal titration calorimetry (ITC) demonstrates the optimal saccharide tether length and the effect of electrostatics on protein affinity, revealing insights into the impact of synthetic design on molecular recognition. The presented studies offer an enhanced understanding of structure‐function relationships governing lectin‐saccharide interactions at the molecular level and guide a systematic approach towards optimizing glyconanoassembly binding parameters. 

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3. Glycopolymer-Wrapped Carbon Nanotubes Show Distinct Interaction of Carbohydrates With Lectins

   https://doi.org/10.3389/fchem.2022.852988  

   DiLillo, Ana M.; Chan, Ka Keung; Sun, Xue-Long; Ao, Geyou (March 2022, Frontiers in Chemistry)

   Glyconanomaterials with unique nanoscale property and carbohydrate functionality show vast potential in biological and biomedical applications. We investigated the interactions of noncovalent complexes of single-wall carbon nanotubes that are wrapped by disaccharide lactose-containing glycopolymers with the specific carbohydrate-binding proteins. The terminal galactose (Gal) of glycopolymers binds to the specific lectin as expected. Interestingly, an increased aggregation of nanotubes was also observed when interacting with a glucose (Glc) specific lectin, likely due to the removal of Glc groups from the surface of nanotubes resulting from the potential binding of the lectin to the Glc in the glycopolymers. This result indicates that the wrapping conformation of glycopolymers on the surface of nanotubes potentially allows improved accessibility of the Glc for specific lectins. Furthermore, it shows that the interaction between Glc groups in the glycopolymers and nanotubes play a key role in stabilizing the nanocomplexes. Overall, our results demonstrate that nanostructures can enable conformation-dependent interactions of glycopolymers and proteins and can potentially lead to the creation of versatile optical sensors for detecting carbohydrate-protein interactions with enhanced specificity and sensitivity. 

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4. Glycocalyx crowding with mucin mimetics strengthens binding of soluble and virus-associated lectins to host cell glycan receptors

   https://doi.org/10.1073/pnas.2107896118  

   Honigfort, Daniel J.; Altman, Meghan O.; Gagneux, Pascal; Godula, Kamil (October 2021, Proceedings of the National Academy of Sciences)

   Membrane-associated mucins protect epithelial cell surfaces against pathogenic threats by serving as nonproductive decoys that capture infectious agents and clear them from the cell surface and by erecting a physical barrier that restricts their access to target receptors on host cells. However, the mechanisms through which mucins function are still poorly defined because of a limited repertoire of tools available for tailoring their structure and composition in living cells with molecular precision. Using synthetic glycopolymer mimetics of mucins, we modeled the mucosal glycocalyx on red blood cells (RBCs) and evaluated its influence on lectin (SNA) and virus (H1N1) adhesion to endogenous sialic acid receptors. The glycocalyx inhibited the rate of SNA and H1N1 adhesion in a size- and density-dependent manner, consistent with the current view of mucins as providing a protective shield against pathogens. Counterintuitively, increasing the density of the mucin mimetics enhanced the retention of bound lectins and viruses. Careful characterization of SNA behavior at the RBC surface using a range of biophysical and imaging techniques revealed lectin-induced crowding and reorganization of the glycocalyx with concomitant enhancement in lectin clustering, presumably through the formation of a more extensive glycan receptor patch at the cell membrane. Our findings indicate that glycan-targeting pathogens may exploit the biophysical and biomechanical properties of mucins to overcome the mucosal glycocalyx barrier. 

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5. Density of Compatible Ligands on the Surface of Food Particles Modulates Sorting Efficiency in the Blue Mussel Mytilus edulis

   https://doi.org/10.3389/fmars.2022.882356  

   Pales Espinosa, Emmanuelle; Eckstein, Margot; Allam, Bassem (May 2022, Frontiers in Marine Science)

   The adhesion between food particles and mucus is a fundamental process in particle sorting in suspension-feeding bivalves that requires specific recognition. Interactions between carbohydrate-binding proteins (lectins) expressed on the feeding organs and carbohydrates present on microbial cell surface can provide this specificity. Microalga cell surface carbohydrates (MCSC) represent unique patterns that can be considered as species-specific fingerprints. In this study, sorting efficiencies in blue mussels Mytilus edulis fed with microalgae having modified MCSC and engineered microspheres coated with target carbohydrates was measured. The nature and quantities of surface carbohydrates required to trigger sorting in mussels was evaluated and the relationship between ligand quantities and sorting efficiency (SE) was determined. Mussels fed with Chlamydomonas which MCSC were blocked with ConA or PEA lectins (affinity to mannose and glucose) led to a significant decrease of the sorting efficiencies, not observed when the lectin UEA (affinity to fucose) was used. The ability of commercial lectins to inhibit sorting was not linear and a threshold was noted between 30 and 45 ug lectins per million algae cells. Further, mussels were fed with microspheres coated with neoglycoproteins. Results showed that glucose-BSA, but not fucose-BSA, has an effect on particle sorting in mussels, and 1.08 x 10 9 molecules of glucose per microspheres, corresponding to a density of 6.99 x 10 6 molecules of glucose per µm 2 , triggers particle selection. These findings support that selection of food particles by mussels rely on the strength of the bond between suspended particle and the mucosal layer that mediate sorting, and that these bonds depend on the quantity of compatible ligands on each particle. 

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