title: Structural analysis of viral infectivity factor of HIV type 1 and its interaction with A3G, EloC and EloB.
abstract: BACKGROUND
  The virion infectivity factor (Vif) is an accessory protein, which is essential for HIV replication in host cells. Vif neutralizes the antiviral host protein APOBEC3 through recruitment of the E3 ubiquitin ligase complex.
  
  
  METHODS
  Fifty thousand Vif models were generated using the ab initio relax protocol of the Rosetta algorithm from sets of three- and nine-residue fragments using the fragment Monte Carlo insertion-simulated annealing strategy, which favors protein-like features, followed by an all-atom refinement. In the protocol, a constraints archive was used to define the spatial relationship between the side chains from Cys/His residues and zinc ions that formed the zinc-finger motif that is essential for Vif function. We also performed centroids analysis and structural analysis with respect to the formation of the zinc-finger, and the residue disposal in the protein binding domains. Additionally, molecular docking was used to explore details of Vif-A3G and Vif-EloBC interactions. Furthermore, molecular dynamics simulation was used to evaluate the stability of the complexes Vif-EloBC-A3G and Vif-EloC.
  
  
  RESULTS
  The zinc in the HCCH domain significantly alters the folding of Vif and changes the structural dynamics of the HCCH region. Ab initio modeling indicated that the Vif zinc-finger possibly displays tetrahedral geometry as suggested by Mehle et al. (2006). Our model also showed that the residues L146 and L149 of the BC-box motif bind to EloC by hydrophobic interactions, and the residue P162 of the PPLP motif is important to EloB binding.
  
  
  CONCLUSIONS
  The model presented here is the first complete three-dimensional structure of the Vif. The interaction of Vif with the A3G protein and the EloBC complex is in agreement with empirical data that is currently available in the literature and could therefore provide valuable structural information for advances in rational drug design.
authors.affiliation: Laboratório de Planejamento e Desenvolvimento de Fármacos, Instituto de Ciências Exatas e Naturais- ICEN e Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, Brazil.
authors.forename: Kauê Santana
authors.initials: KS
authors.lastname: da Costa
authors.affiliation: Faculdade de Biotecnologia, Universidade Federal do Pará, Belém, Brazil.
authors.forename: Elcio
authors.initials: E
authors.lastname: Leal
authors.affiliation: Laboratório de Planejamento e Desenvolvimento de Fármacos, Instituto de Ciências Exatas e Naturais- ICEN e Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, Brazil.
authors.forename: Alberto Monteiro
authors.initials: AM
authors.lastname: dos Santos
authors.affiliation: Laboratório de Planejamento e Desenvolvimento de Fármacos, Instituto de Ciências Exatas e Naturais- ICEN e Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, Brazil.
authors.forename: Anderson Henrique
authors.initials: AH
authors.lastname: Lima e Lima
authors.affiliation: Laboratório de Planejamento e Desenvolvimento de Fármacos, Instituto de Ciências Exatas e Naturais- ICEN e Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, Brazil.
authors.forename: Cláudio Nahum
authors.initials: CN
authors.lastname: Alves
authors.affiliation: Laboratório de Planejamento e Desenvolvimento de Fármacos, Instituto de Ciências Exatas e Naturais- ICEN e Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, Brazil ; Faculdade de Biotecnologia, Universidade Federal do Pará, Belém, Brazil.
authors.forename: Jerônimo
authors.initials: J
authors.lastname: Lameira
mesh_terms: D000071478:APOBEC Deaminases; D001665:Binding Sites; D003564:Cytidine Deaminase; D043525:Cytosine Deaminase / Q000378:metabolism; D015497:HIV-1 / Q000472:pathogenicity*; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D009010:Monte Carlo Method; D011485:Protein Binding; D017510:Protein Folding; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D037521:Virulence Factors / Q000737:chemistry / Q000378:metabolism*; D016335:Zinc Fingers; D054320:vif Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000378:metabolism
chemical_list: D037521:Virulence Factors; D054320:vif Gene Products, Human Immunodeficiency Virus; C514847:vif protein, Human immunodeficiency virus 1; D044767:Ubiquitin-Protein Ligases; D043525:Cytosine Deaminase; D000071478:APOBEC Deaminases; C502889:APOBEC3 proteins, human; D003564:Cytidine Deaminase