The APOBEC3's (A3G, A3F and possibly A3H) are cellular DNA cytosine deaminases that are key innate anti-viral agents, particularly in response to HIV-1. Although the structures of the catalytic domains of these important enzymes are beginning to be elucidated, the details of their specificities and interactions with other cellular and viral macromolecules still remains to be determined. In this proposal we are using a combination of crystallographic, molecular modeling, calorimetry, mass spectrometry and viral studies to characterize the domains of the various APOBEC3's, both intra-molecularly within their domains and inter-molecularly with their interactions with HIV-1 Vif. PUBLIC HEALTH RELEVANCE: When HIV infects the human body, many molecules attempt to prevent the virus from spreading. One such family of proteins are called the APOBEC3's. These proteins attempt to change the viral RNA, to make the virus less infectious. We are using molecular biophysical techniques to visualize these interactions in atomic detail, so that they can eventually be targeted for drug therapy.