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 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 APOBEC3G. To perform this study we have assembled an interdisciplinary team of structural biologists and molecular virologists. We propose to use a combination of cross-linking, proteolysis, and mass spectrometry to determine particular specific interactions of Vif, APOBEC3G and their complex in solution at equilibrium. We propose three specific aims to begin this research track: (1) Elucidate the binding interfaces in HIV-1 Vif oligomerization; (2) Elucidate the binding interfaces in APOBEC3G oligomerization; (3) Elucidate the binding interfaces between HIV-1 Vif and APOBEC3G. ? ? ?
| Auclair, Jared R; Somasundaran, Mohan; Green, Karin M et al. (2012) Mass spectrometry tools for analysis of intermolecular interactions. Methods Mol Biol 896:387-98 |
| Shandilya, Shivender M D; Nalam, Madhavi N L; Nalivaika, Ellen A et al. (2010) Crystal structure of the APOBEC3G catalytic domain reveals potential oligomerization interfaces. Structure 18:28-38 |
| Auclair, Jared R; Green, Karin M; Shandilya, Shivender et al. (2007) Mass spectrometry analysis of HIV-1 Vif reveals an increase in ordered structure upon oligomerization in regions necessary for viral infectivity. Proteins 69:270-84 |
