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Online Journal of Bioinformatics ©
Volume 11 (1): 19-33, 2010.
Structural and docking analysis of HIV-1 integrase and Transportin-SR2 interaction:
Is this a more general and specific route for retroviral nuclear import and its regulation?
Sergey Shityakov1,2,*, Axel Rethwilm1, and Thomas Dandekar1,2
1 Institute for Virology and Immunobiology, University of Wurzburg, Versbacher Str. 7, 97078 Wurzburg, Germany 2 Dept. of Bioinformatics, Biocenter University of Wurzburg, 97074 Wurzburg,Germany, *corresponding author.
Shityakov S, Rethwilm A, Dandekar T., Structural and docking analysis of HIV-1 integrase and Transportin-SR2 interaction: Is this a more general and specific route for retroviral nuclear import and its regulation? Onl J Bioinform., 11 (1):19-33, 2010. HIV-1 integrase has NLS (nuclear localization signals) which plays an important role in intranuclear transport of viral PIC (preintegration complex). The exact mechanisms of PIC formation and its inter-nuclear transport are not known. It was shown that NLSs bind to the cell transport machinery e.g. proteins of nuclear pore complex such as transportins. We investigated the interaction of this viral protein with proteins of the nuclear pore complex (transportin-SR2). We showed reasons why transportin-SR2 is the nuclear import protein for HIV-1 integrase and not transportin-SR1: (i) 3D alignments identify differences between transportin-SR1 and transportin-SR2. (ii) Rigid protein-protein docking showed key domain interactions and hydrogen bonds available to transportin-SR2. (iii) Flexible receptor-ligand docking was performed to reveal crucial amino acid residues involved in this hydrogen bond formation. These results are discussed to better understand this specific and efficient retroviral transport route comparing the interactions of related retroviruses (SIV, HIV-2, PFV etc.) with their cognate transport proteins, NLS sequences and kinase binding motifs.
Key words: Docking; Nuclear import; Transportin-SR1; Nuclear localization, signal; HIV-1 integrase.