The structure and functional interactions of HIV-1 Vif are still unknown in molecular and atomic detail, even though it is clear that this protein plays an important role in regulating virus replication and infection. This role is essential and therefore HIV- 1 Vif represents a novel target to initiate inhibitor design. Our objective is to elucidate the structure of HIV- 1 Vif and its functional partners and thereby begin the investigation of the hypothesis that HIV-1 Vif might be a viable anti-viral target, either by inhibiting its function directly, its oligomerization state or through disrupting its cellular partners such as CEM15. We propose three specific aims to begin this research track: 1) Structural studies of HIV-1 Vif (which includes determining the conditions under which the protein is folded, what the predominant oligomeric state of the protein is, and crystallization screens toward the determination of a three-dimensional structure) 2) Structural studies of the cellular factor which HIV-1 Vif may interfere with, CEM15 (ABOBEC3G) (express, purify, determine the conditions under which the protein is folded and crystallization screens) and 3) In vitro functional studies of possible interactions between HIV-1 Vif and CEM 15 and between HIV-1 Vif and HIV-1 protease. To perform this study we have assembled an interdisciplinary team of structural biologists and molecular virologists. The data accumulated will elucidate the molecular properties of HIV-1 Vif and CEM 15 and will provide additional data for an R01 application.