Structural thermodynamics of complex carbohydat recognition by proteins

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The specific binding of complex oligosaccharides by proteins is at the heart of numerous biological recognition processes. It is central to physiological cell-cell interactions, as well as tumor formation in animals, the establishment of symbiotic interactions between plants and bacteria, and many infection processes throughout all kingdoms of biology. Structural and biophysical data on such recognition processes are scarce, as the interaction partners often are not accessible in biochemical quantities. We have isolated several bacteriophage tailspike proteins recognizing complex oligosaccharide structures on the cell surfaces of the bacterial host cells of the phages and determined high-resolution crystal structures of the corresponding protein-carbohydrate complexes. Biochemical amounts of the binding partners are easily accessible in high purity from natural sources. Moreover, the proteins have high thermostability. This makes these systems exceptionally well suited for structural thermodynamics studies. To investigate the driving forces in the formation of protein complexes with complex oligosaccharides, we will undertake a thorough thermodynamic characterization of the binding interactions between tailspike proteins and oligosaccharides using a combination of biochemical and biophysical methods. Mutant proteins and oligosaccharides of different length and composition will be employed to identify sources of specificity. Our data will help understanding and predicting biological recognition processes and will be highly relevant for molecular medicine and biotechnology.