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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Taltynov, Oliver Strelkov, Sergei V. Demeulemeester, Jonas Tsirkone, Vicky G. Debyser, Zeger Gerard, Melanie Christ, Frauke Weeks, Stephen D. De Houwer, Stéphanie |
| Description | Author Affiliation: Taltynov O ( Laboratory for Molecular Virology and Gene Therapy, KU Leuven, B-3000 Leuven, Belgium.) |
| 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 before 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 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 preintegration complex 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. Although 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 that is in excellent agreement with the experimental small angle x-ray scattering data. |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | Journal of Biological Chemistry |
| Issue Number | 35 |
| Volume Number | 288 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date | 2013-08-30 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Models, Molecular Multiprotein Complexes Chemistry Protein Multimerization Beta Karyopherins Ran GTP-Binding Protein Active Transport, Cell Nucleus Genetics HIV Integrase Metabolism HIV-1 Protein Binding Protein Structure, Tertiary Research Support, Non-U.S. Gov't Biochemistry Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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