Structural Biology of Polysialic Acid Recognition

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The aim of the application is to structurally investigate the binding of polysialic acids to various cellular proteins, and to characterize these interactions using affinity measurements. The application focuses on the one hand on Siglecs (sialic acid-binding receptors and signaling molecules) and on the other hand on CXCL12-type chemokines. Both protein types bind polysialic acids, and in both cases the binding is highly relevant for the function of the respective protein. In preliminary work, we already have determined a high-resolution crystal structure of a central domain of the Siglec-11 protein, and various longer protein fragments have been expressed and purified. In terms of methods, protein biochemistry and structure elucidation (NMR spectroscopy, X-ray crystallography) as well as various affinity measurement methods will be used. The project features tight collaborations with several other projects, most importantly projects 4, 5 and 6.