To initiate infection and spread within the host tissues, L. monocytogenes, a food-borne, facultative intracellular pathogen, induces its own uptake into normally nonphagocytic host cells. Internalin (InlA) and InlB, two listerial proteins, have been implicated in this process. InlA is responsible for the first step of infection by binding to E-cadherin located on intestinal epithelial cells. InlB, required for uptake into numerous other mammalian tissues, binds to the receptor tyrosine kinase Met initiating its autophosphorylation and inducing uptake. The complex of InlA/E-cadherin has successfully been crystallized and its structure solved. We propose to build on these results to strengthen the interaction between the molecules thereby providing a tool to investigate the process of InlA-induced internalisation and the route of E-cadherin-mediated outside-in signalling. The Met receptor is crucial for embryonic development, tissue regeneration and cancer. Analysing the complex of InlB/Met by X-ray crystallography would yield the first structure of the Met extracellular domain and would reveal the InlB-induced mechanism of Met dimerization and autophosphorylation. Identifying binding partners of other cell-surface proteins (InlE to InlH, FbpA, LMO1666, LMO1076) and analysing them structurally will provide further insight into the mechanisms employed by Listeria monocytogenes to exploit the host's cells.
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