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

作     者：Congjie Zhai Ling Ma Zhixin Zhang Jiwei Ding Jing Wang Yongxin Zhang Xiaoyu Li Fei Guo Liyan Yu Jinming Zhou Shan Cen 

作者机构：Institute of Medicinal Biotechnology Chinese Academy of Medical Science Institute of Pathogen Biology Chinese Academy of Medical Science 

出 版 物：《Acta Pharmaceutica Sinica B》 (药学学报（英文版）)

年 卷 期：2017年第7卷第5期

页      面：571-582,616页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 10[医学] 

基　　金：supported by 973 program (2012CB911102 CS) National Megaproject for Innovative Drugs (2012ZX09301002-001-015 and 2012ZX09301002-005-002 CS) National Mega-Project for Infectious Disease (2013ZX1000 4601-002 CS) The National Natural Science Foundation of China (81271844 ZJM and 31470272 CS) 

主　　题：HIV Vif APOBEC3G Motif Modeling hA3G–Vif complex hA3G dimer 

摘      要：Human APOBEC3G(h A3G) 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 h A3G–Vif complex. The molecular modeling study revealed that the loop7 motif of hA3G appears on the interfaces of both the h A3G–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 ***, we presented evidence for the important roles of the loop7 motif, especially the central residues within the region, in hA3G dimerization, h A3G–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 A3 G degradation by targeting the putative site around loop7.