title: Influence of ligand presentation density on the molecular recognition of mannose-functionalised glyconanoparticles by bacterial lectin BC2L-A.
abstract: Polyvalent carbohydrate-protein interactions play a key role in bio- and pathological processes, including cell-cell communication and pathogen invasion. In order to study, control and manipulate these interactions gold nanoparticles have been employed as a 3D scaffold, presenting carbohydrate ligands in a multivalent fashion for use as high affinity binding partners and a model system for oligosaccharide presentation at biomacromolecular surfaces. In this study, the binding of a series of mannose-functionalised gold nanoparticles to the dimeric BC2L-A lectin from Burkholderia cenocepacia has been evaluated. BC2L-A is known to exhibit a high specificity for (oligo)mannosides. Due to the unique structure and binding nature of this lectin, it provides a useful tool to study (oligo)saccharides presented on multivalent scaffolds. Surface plasmon resonance and isothermal titration calorimetric assays were used to investigate the effect of ligand presentation density towards binding to the bacterial lectin. We show how a combination of structural complementarities between ligand presentation and lectin architecture and statistical re-binding effects are important for increasing the avidity of multivalent ligands for recognition by their protein receptors; further demonstrating the application of glyconanotechnology towards fundamental glycobiology research as well as a potential towards biomedical diagnostics and therapeutic treatments.
authors.affiliation: Centre de Recherche sur les Macromolécules Végétales (CERMAV - CNRS), affiliated with Université Joseph Fourier Grenoble and ICMG, BP 53, 38041, Grenoble, France.
authors.forename: Michael
authors.initials: M
authors.lastname: Reynolds
authors.forename: Marco
authors.initials: M
authors.lastname: Marradi
authors.forename: Anne
authors.initials: A
authors.lastname: Imberty
authors.forename: Soledad
authors.initials: S
authors.lastname: Penadés
authors.forename: Serge
authors.initials: S
authors.lastname: Pérez
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D057508:Burkholderia cenocepacia / Q000737:chemistry / Q000378:metabolism; D008024:Ligands; D008358:Mannose / Q000378:metabolism*; D037241:Mannose-Binding Lectins / Q000737:chemistry / Q000378:metabolism*; D053768:Metal Nanoparticles / Q000737:chemistry*; D008969:Molecular Sequence Data; D011485:Protein Binding; D013379:Substrate Specificity; D020349:Surface Plasmon Resonance
chemical_list: D001426:Bacterial Proteins; D008024:Ligands; D037241:Mannose-Binding Lectins; D008358:Mannose