LipoPolySaccharides are a hallmark of Gram-negative bacteria and their presence at the cell surface is key for bacterial integrity. As surface exposed components, they are recognized by immunity C-type lectin receptors present on Antigen Presenting Cells. Human Macrophage Galactose Lectin binds E. coli surface that presents a specific glycan motif. Nevertheless, this high affinity interaction occurs regardless of the integrity of its canonical calcium-dependent glycan binding site. Nuclear Magnetic Resonance of MGL carbohydrate recognition domain and complete extracellular domain revealed a new glycan binding site opposite to the canonical site. A model of trimeric Macrophage Galactose Lectin was determined based on a combination of Small Angle X-ray scattering and Alphafold. A disulphide bond positions the Carbohydrate Recognition Domain perpendicular to the coiled-coil domain. This unique configuration for a C-type lectin orients the six glycan sites of MGL in an ideal position to bind LipoPolySaccharides at the bacterial surface with high avidity.
The unique 3D arrangement of macrophage galactose lectin enables Escherichia coli lipopolysaccharide recognition through two distinct interfaces. Abbas M, Maalej M, Nieto-Fabregat F, Thépaut M, Kleman JP, Ayala I, Molinaro A, Simorre JP, Marchetti R, Fieschi F, Laguri C. Proceedings of the National Academy of Sciences Nexus 2023 ; 2(9):pgad310.
Contact : C. Laguri (IBS/Membrane and Pathogens Group)