Human APOBEC3G (hA3G) is a cytidine deaminase which inhibits HIV-1 replication.The HIV-1 accessory protein viral infectivity factor (Vif) counteracts with hA3G by targeting it for proteasomal degradation.In this work,we constructed and optimized molecular models of the hA3G dimer and the hA3G-Vif complex.The molecular modeling study revealed that the loop7 motif of hA3G appears on the interfaces of both the hA3G-Vif complex and the hA3G dimer.Biochemical analysis provided evidence suggesting that binding of Vif to hA3G results in steric blocking of hA3G dimerization,implying that monomeric hA3G serves as a substrate for Vif-mediated degradation.Furthermore,we presented evidence for the important roles of the loop7 motif,especially the central residues within the region,in hA3G dimerization,hA3G-Vif interaction,Vif-mediated hA3G degradation as well as subcellular localization of hA3G.This work highlights a multiple-task interface formed by loop7 motif,which regulates biological function of hA3G,thus providing the feasibility of the strategy of blocking Vif-mediated A3G degradation by targeting the putative site around loop7.