HIV accessory protein

Schug, A. Herges, T. Wenzel, W., All-atom folding of the three-helix HIV accessory protein with an adaptive parallel tempering method, Proteins-Struct. Funct. Bioinform. 2004, 57, 792-798... 

Summary. We recently developed an all-atom free energy force field (PFFOl) for protein structure prediction with stochastic optimization methods. We demonstrated that PFFOl correctly predicts the native conformation of several proteins as the global optimum of the free energy surface. Here we review recent folding studies, which permitted the reproducible all-atom folding of the 20 amino-acid trp-cage protein, the 40-amino acid three-helix HIV accessory protein and the sixty amino acid bacterial ribosomal protein L20 with a variety of stochastic optimization methods. These results demonstrate that all-atom protein folding can be achieved with present day computational resources for proteins of moderate size. 

Figure 1. Overlay of the native(red) and folded (blue) structures of trp-cage protein [35], the HIV accessory protein [13] and the bacterial ribosomal protein L20 [14],...

Table 1. Energies (in kcal/mol) of the 10 lowest energy decoys obtained in the basin hopping simulations of the HIV accessory protein. The table shows the backbone RMS deviation to the NMR structure and secondary structure content. The first row designates the secondary structure content of the NMR structure.

We also performed a simulation of the HIV accessory protein using the adapted parallel tempering method [13]. We used 20 processors of an INTEL XEON PC cluster and ran the simulation for a total of 30 x 10 energy evaluations for each configuration, which corresponds to approximately 500 CPU hours on an 2.4 GHz INTEL XEON processor. All simulations were started... 

Because HIV-1 is a human pathogen, there is some concern about the use of HIV-1-based lentiviral vectors. The current HIV-1 lentiviral vector system is deprived of all accessory proteins (except rev) and viral sequences in the vectors have been minimized therefore, replication of these vectors is highly disabled and the possibility of homologous recombination is minimized. In addition, codon-optimization of the packaging construct further decreases the risk of homologous recombination. Furthermore, changes in the codons makes the production of the structural proteins independent of rev, and therefore additional viral sequences (RRE) can be eliminated from the packaging construct (82). 

HIV is a retrovirus in which the virus uses the body s cellular machinery to transform RNA to DNA. The number of helper T cells is dramatically reduced thereby lowering the body s immune response. GP-120 is essential to the virus binding to the cell surface receptor for entry into the cell. 14-3-3-0 is specifically implicated in the G2 checkpoint for cell cycle arrest for the HIV-1 VPR (viral protein R) accessory protein, which is associated with cell death since VPR is necessary for viral infection of helper T cells (Bolton et al. 2008). 14-3-3-0 can bind to several cyclin-dependent kinases that regulate the cell cycle leading to overall neurodegeneration in this immune disorder. Lipid peroxidation of the 14-3-3 family of proteins may cause reduced interaction with protein kinases, which can result in reduced signal transduction by which protein synthesis, cell cycle regulation, and DNA repair may be affected. 

Accessory regulatory genes. HIV and some related retroviruses such as FTTLV-1 (which causes rare T-cell leukemias)719 are distinguished from other retroviruses by a marked increase in the rate of DNA transcription within infected cells as compared with uninfected cells. This is thought to be a result of synthesis of virally encoded proteins that are trans-acting... 

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