Studies on Protein Lipidation

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PROJECT SUMMARY To elucidate the antiviral mechanism of S-palmitoylated IFITMs (1, 2 and 3) in host immunity against viruses, we propose to perform detailed biochemical, biophysical and cellular studies of these lipidated immune effectors in this grant renewal. For biochemical and structural studies of IFITMs, we will perform computational modeling and reconstitute site-specifically lipidated IFITM3 in vitro (Aim 1). Moreover, we have discovered direct interactions of IFITMs with specific cellular lipids and will investigate their significance biochemically in vitro and in mammalian cells during virus infections (Aim 2). Lastly, we will investigate S-palmitoylated IFITM interactions with key cellular factors involved their regulation and antiviral activity (Aim 3). These studies should help determine how IFITMs prevent virus entry and elucidate biochemical mechanisms by which site-specific lipidation controls membrane protein structure and function in host immunity. Determining the mechanisms that control S-palmitoylated IFITMs function is crucial for understanding host immunity and may reveal new strategies for combatting virus infection in humans.