Identification and characterization of loop7 motif and its role in regulating biological function of human APOBEC3G through molecular modeling and biological assay

• 来源期刊: 药学学报（英文版）
• 关键词: HIV Vif APOBEC3G Motif Modeling hA3G-Vif complex hA3G dimer
• 年，卷（期）: 2017,（5）
• 页码范围: 571-582
• 页数: 12页
• 语种: 英文

摘要

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.