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Interaction of TRN-SR 2 with Ran 1 Interaction of Transportin-SR 2 with Ras-related nuclear protein ( Ran ) GTPase *
| Content Provider | Semantic Scholar |
|---|---|
| Author | Taltynov, Oliver Demeulemeester, Jonas Christ, Frauke Houwer, Stéphanie De Tsirkone, Vicky G. Gérard, Mélanie Weeks, Stephen D. Strelkov, Sergei V. Debyser, Zeger |
| Copyright Year | 2013 |
| 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 HIV1 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 GDPand 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. INTRODUCTION The human immunodeficiency virus type 1 (HIV-1) and other lentiviruses have the capacity to infect non-dividing cells such as macrophages through an active nuclear import mechanism (1, 2). Nuclear import is particularly important in the pathogenesis of HIV-1, because non-dividing cells are a key reservoir of virus in infected individuals. After viral entry and partial uncoating the reverse transcriptase (RT) produces a double stranded DNA copy of the viral RNA genome. During its migration to the nucleus the reverse transcription complex is gradually transformed into the preintegration complex (PIC). Capsid (CA) proteins remain at least partially associated with http://www.jbc.org/cgi/doi/10.1074/jbc.M113.484345 The latest version is at JBC Papers in Press. Published on July 22, 2013 as Manuscript M113.484345 Copyright 2013 by The American Society for Biochemistry and Molecular Biology, Inc. at JOHNSON & JOHNSON on August 8, 2013 http://www.jbc.org/ Downloaded from Interaction of TRN-SR2 with Ran |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | https://core.ac.uk/download/pdf/34573274.pdf |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
