BC2L-C N-Terminal Lectin Domain Complexed with Histo Blood Group Oligosaccharides Provides New Structural Information.
Rafael BermeoAnna BernardiAnnabelle VarrotPublished in: Molecules (Basel, Switzerland) (2020)
Lectins mediate adhesion of pathogens to host tissues, filling in a key role in the first steps of infection. Belonging to the opportunistic pathogen Burkholderia cenocepacia, BC2L-C is a superlectin with dual carbohydrate specificity, believed to mediate cross-linking between bacteria and host cells. Its C-terminal domain binds to bacterial mannosides while its N-terminal domain (BCL2-CN) recognizes fucosylated human epitopes. BC2L-CN presents a tumor necrosis factor alpha (TNF-) fold previously unseen in lectins with a novel fucose binding mode. We report, here, the production of a novel recombinant form of BC2L-CN (rBC2L-CN2), which allowed better protein stability and unprecedented co-crystallization with oligosaccharides. Isothermal calorimetry measurements showed no detrimental effect on ligand binding and data were obtained on the binding of Globo H hexasaccharide and l-galactose. Crystal structures of rBC2L-CN2 were solved in complex with two blood group antigens: H-type 1 and H-type 3 (Globo H) by X-ray crystallography. They provide new structural information on the binding site, of importance for the structural-based design of glycodrugs as new antimicrobials with antiadhesive properties.
Keyphrases
- lymph node metastasis
- rheumatoid arthritis
- induced apoptosis
- squamous cell carcinoma
- endothelial cells
- binding protein
- gene expression
- high resolution
- cell cycle arrest
- healthcare
- red blood cell
- dendritic cells
- small molecule
- immune response
- big data
- signaling pathway
- gram negative
- biofilm formation
- protein protein
- candida albicans
- endoplasmic reticulum stress
- computed tomography
- magnetic resonance
- induced pluripotent stem cells
- pseudomonas aeruginosa
- staphylococcus aureus
- pluripotent stem cells
- amino acid