title: Three-dimensional structure of HIV-1 VIF constructed by comparative modeling and the function characterization analyzed by molecular dynamics simulation.
abstract: VIF is one of the six accessory proteins of HIV-1. It has been shown to be necessary for the survival of HIV-1 in the human body and for the retention of viral infectivity. It is strongly expected that a new therapeutic strategy against HIV-1 infection could be realized by blocking the biological pathway to VIF. In this paper, a three-dimensional model of VIF was constructed by comparative modeling based on two templates, VHL and NarL, which were used to construct the C-terminal domain and N-terminal domain of VIF, respectively. A model of the VIF-ElonginB-ElonginC complex was constructed, and molecular dynamics simulations were used to investigate the interactions between VIF and ElonginB-ElonginC. Mutagenesis was used to identify the function of some conserved residues in the putative SOCS-box. The results showed that the mutations of the critical residues led to the disruption of the interactions between VIF and ElonginB-ElonginC, consistent with experimental observations. These novel models of VIF and its complex has therefore provided structural information for investigating the function of VIF at the molecular level.
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100083, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Lv
authors.forename: Zhenming
authors.initials: Z
authors.lastname: Liu
authors.forename: Hongwei
authors.initials: H
authors.lastname: Jin
authors.forename: Xianghui
authors.initials: X
authors.lastname: Yu
authors.forename: Liangren
authors.initials: L
authors.lastname: Zhang
authors.forename: Lihe
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000595:Amino Acid Sequence; D003198:Computer Simulation; D016346:Gene Products, vif / Q000737:chemistry*; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017433:Protein Structure, Secondary
chemical_list: D016346:Gene Products, vif