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OJBTM
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.
ABSTRACT
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? Online J Bioinformatics, 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.