During years, the insolubility of A3G did not allowed to solve a 3D structure. By enhancing A3G solubility by sequence engineering (sA3G) and identifying optimal binding short RNA (RNA20), Vif-human complexes were solved by cryoEM as asymmetric hetero-dimers 9 (Figure ). Each of the two sA3G monomers binds: two Vifs (Vif blue binding the sA3G N-terminal RNA domain and Vif red binding the sA3G C-terminal deamination domain), two CBF and 1 RNA20 (Vif blue Vif red -sA3G-2CBF-RNA). Most probably, A3G binds RNA during its translation and contributes to the enhancement of affinities among the proteins on the complexes. Similar model interfaces have been predicted among other A3G complexes from different sources and laboratories . The proposed heterodimer model was further assessed because it included correct binding predictions to human ubiquitin-ligase .