A3G is a single-stranded DNA cytosine deaminase that can restrict HIV-1 infection by mutating HIV-1 genome. HIV-1 developed a counter defense mechanism by which virion infectivity factor (Vif) leads the degradation of A3G through ubiquitin-proteasome pathway. Our ultimate goal is to generate small compounds which inhibit the degradation of A3G. We have determined structures of two functional domains of A3G, including the VIf-binding domain and the catalytic domain. We have been working toward the structure determination of the A3G-Vif E3 ubiquitin ligase complex that will provide epitopes to be targeted by small compounds which inhibit formation of the complex. The A3G-Vif E3 ubiquitin ligase complex contains 6 proteins, and therefore it is challenging for any structural study. We are developing and optimizing biochemical and spectroscopic techniques to overcome the challenge.
| Pan, Yangang; Sun, Zhiqiang; Maiti, Atanu et al. (2017) Nanoscale Characterization of Interaction of APOBEC3G with RNA. Biochemistry 56:1473-1481 |
| Kouno, Takahide; Silvas, Tania V; Hilbert, Brendan J et al. (2017) Crystal structure of APOBEC3A bound to single-stranded DNA reveals structural basis for cytidine deamination and specificity. Nat Commun 8:15024 |
