A mytilectin from Mytilus californianus: Study of its unique galactoside interactions, oligomerization patterns, and...

In marine invertebrate such as bivalve mollusks, lectins play a critical rol in the immune system, defending against pathogens. A novel family of lectins, named mytilectins, has been discovered in these organisms. They are noted for their antifungal, antibacterial, and anticancer properties, suggesting substantial potential for biomedical and biotechnological applications. In this study, we describe rMcL-1, a mytilectin from the mussel Mytilus californianus. We explored the binding mechanisms using crystallographic data with five different galactosides, highlighting rMcL-1's preference for α-galactosides. By analyzing amino acid variations in its three carbohydrate-binding sites, we assessed their impact on binding affinity and specificity. Interestingly, rMcL-1 is capable of binding non-galactosides, and ligands with lower affinity, such as lactose, induce significant conformational changes in specific binding sites. A novel binding site at the dimer interface was identified in the presence of lactulose. Co-crystallization experiments demonstrated that ligand binding promotes oligomerization, with the resulting quaternary structure varying depending on the sugar involved. An analysis of the puckering parameters and transglycosidic dihedral angles of the glycan moieties associated with oligomeric rMcL-1 revealed consistent conformational preferences in lactulose moieties, while raffinose and lactose exhibited greater variability. Additionally, rMcL-1 exhibited antifungal activity against several phytopathogenic fungi, including Alternaria alternata, Fusarium oxysporum, Phytophthora capsici, and Pythium aphanidermatum. Overall, this study enhances our understanding of the molecular mechanisms underlying the diverse activities of mytilectins and may aid in the design of artificial lectins with specific and improved binding properties.