PROTEIN-CARBOHYDRATE INTERACTION: STRUCTURAL AND THERMODYNAMIC CHARACTERISATION OF HIGH AFFNITY BINDING BETWEEN LECTINS FROM PATHOGENS AND HOST CARBOHYDRATES

M. Wimmerová^1,2, M. Pokorná¹, C. Sabin³, S. Perret³, J. Adam¹, E.P. Mitchell⁴,
A. Imberty³

¹National Centre for Biomolecular Research and ²Department of Biochemistry,
Faculty of Science, Masaryk University, Kotlarska 2, 611 37 Brno, Czech Republic

³CERMAV-CNRS, 601 rue de la Chimie, BP 53, 38041 Grenoble, France

⁴ESRF, Experiments Division, BP 220, 38043 Grenoble, France

e‑mail:michaw@chemi.muni.cz

Carbohydrate-mediated recognition plays an important role in the ability of pathogenic bacteria to adhere to the surface of the host cell in the first step of their invasion and infectivity. Lectin-carbohydrate interactions are usually characterised by a low affinity for monovalent ligands that is balanced by multivalency resulting in high avidity for complex glycans or cell surfaces. Usually, a millimolar affinity is observed for plant lectin binding to monosaccharides. In contrast, bacterial lectins involved in pathogenesis display much higher affinity than that observed for plant or animal lectins [1].

Contribution is focused on bacterial lectins from Pseudomonas aeruginosa and their homologues from other pathogens displaying sub-micromolar range affinity towards their carbohydrate ligands. The combination of X-ray crystallography and isothermal titration microcalorimetry approaches is used to decipher the structural and thermodynamical basis for high affinity binding of these lectins to host carbohydrates. Discovery of a three amino acid motif of the „ligand binding loop” that is responsible for lectin sugar preferences toward different monosaccharides will be discussed.

[1] A. Imberty, E.P. Mitchell & M. Wimmerová, Curr. Opin. Struct. Biol., 15, (2005), 523