P8 - Structural biology of polysialic acid recognition

The longer-term objective of the work proposed here is to achieve an understanding of the parameters that govern the recognition of polysialic acid by proteins, and to use this knowledge for designing inhibitory and/or antagonistic ligands in selected cases. In the first part of this project, we will determine the structural basis of polysialic acid interactions by two sialic acid-binding immunoglobulin-like lectins, human Siglec-11 and murine Siglec-E. Both proteins are inhibitory receptors documented to bind polysialic acid, but structural information is not available for either interaction. In contrast to human Siglec-11, murine Siglec-E can also bind sialyloglycans with sialic acids in other linkages, indicating significant specificity differences between the two Siglecs. In the second part of this project, we will use an already established interaction between the adenovirus 52 fiber knob and polysialic acid to establish rules of polysialic acid engagement and to engineer higher-affinity interactions that will allow this virus to efficiently target polysialic acid-bearing cells.