The unique three-dimensional arrangement of Macrophage Galactose Lectin enables E. coli LipoPolySaccharides recognition through two distinct interfaces

Abbas, M.; Maalej, M.; Nieto Fabregat, F.; Thepaut, M.; Kleman, J.-p.; Ayala, I.; Molinaro, A.; Simorre, J.-P.; Marchetti, R.; Fieschi, F.; Laguri, C.

doi:10.1101/2023.03.02.530591

bioRxiv · 10.1101/2023.03.02.530591

The unique three-dimensional arrangement of Macrophage Galactose Lectin enables E. coli LipoPolySaccharides recognition through two distinct interfaces

Abbas, M.·Maalej, M.·Nieto Fabregat, F.·Thepaut, M.·Kleman, J.-p.·Ayala, I.·Molinaro, A.·Simorre, J.-P.·Marchetti, R.·Fieschi, F.·Laguri, C.

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Abstract

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.

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Abbas, M., Maalej, M., Nieto Fabregat, F., Thepaut, M., Kleman, J.-p., Ayala, I., Molinaro, A., Simorre, J.-P., Marchetti, R., Fieschi, F., Laguri, C.. 2023-03-02. The unique three-dimensional arrangement of Macrophage Galactose Lectin enables E. coli LipoPolySaccharides recognition through two distinct interfaces. https://doi.org/10.1101/2023.03.02.530591

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