Title: Interaction of Transportin-SR2 with Ras-related nuclear protein (Ran) GTPase
Authors: Taltynov, Oliver
Demeulemeester, Jonas
Christ, Frauke
De Houwer, Stéphanie
Tsirkone, Vicky
Gérard, Melanie
Weeks, Stephen
Strelkov, Sergei
Debyser, Zeger # ×
Issue Date: Aug-2013
Publisher: American Society for Biochemistry and Molecular Biology
Series Title: Journal of Biological Chemistry vol:288 issue:35 pages:25603-25613
Abstract: The human immunodeficiency virus type 1 (HIV-1) and other lentiviruses are capable of infecting non-dividing cells and therefore need to be imported into the nucleus prior to integration into the host cell chromatin. Transportin-SR2 (TRN-SR2, Transportin-3, TNPO3) is a cellular karyopherin implicated in nuclear import of HIV-1. A model in which TRN-SR2 imports the viral preintegration complex (PIC) into the nucleus is supported by direct interaction between TRN-SR2 and HIV-1 integrase (IN). Residues in the C-terminal domain of HIV-1 IN that mediate binding to TRN-SR2 were recently delineated. As for most nuclear import cargoes, the driving force behind HIV-1 PIC import is likely a gradient of the GDP- and GTP-bound forms of Ran, a small GTPase. In this study we offer biochemical and structural characterization of the interaction between TRN-SR2 and Ran. By size exclusion chromatography we demonstrate stable complex formation of TRN-SR2 and RanGTP in solution. Consistent with the behavior of normal nuclear import cargoes, HIV-1 IN is released from the complex with TRN-SR2 by RanGTP. While in concentrated solutions TRN-SR2 by itself was predominantly present as a dimer, the TRN-SR2-RanGTP complex was significantly more compact. Further analysis supported a model wherein one monomer of TRN-SR2 is bound to one monomer of RanGTP. Finally, we present a homology model of the TRN-SR2-RanGTP complex, which is in excellent agreement with the experimental SAXS data.
ISSN: 0021-9258
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular Virology and Gene Therapy
Pharmaceutical and Pharmacological Sciences @ Kulak (-)
× corresponding author
# (joint) last author

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