The long-term goals of this project are to provide a structural foundation for understanding the process of pramyxovirus infection, including the specificity of cell recognition and initiation of paramyxovirus infection, including the specificity of cell recognition and initiation of membrane fusion events. The proposed studies are focused on elucidating the relationship of F protein structural states to potential mechanisms of membrane fusion. Studies of the influence virus HA have contributed greatly to our understanding of the analogous recognition and membrane fusion mechanisms of orthomyxoviruses. However, the crystal structure of the SV5 F1 core in particular has shown that new insights can be gained from the study of other viral fusion proteins. Many outstanding questions remain to be clarified in paramyxovirus mediated entry into cells, including the molecular basis for its initiation, the role of potential """"""""metastable"""""""" conformational states in the F proteins, and the energetics of bilayer fusion. In collaboration with the Lamb Laboratory at Northwestern, we will be able to take both a structural and functional approach to understanding these processes. The results of these studies will provide novel information on protein-mediated membrane fusion events that will have significant implications in the development of new anti-viral medications. The observation of structural similarities in viral and cellular protein complexes involved in membrane fusion further suggests that studies of the paramyxovirus F proteins will contribute to our fundamental understanding of a process common to all cells.
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