Assembly of prototype foamy virus strand transfer complexes on product DNA bypassing catalysis of integration
Open Access
- 25 September 2012
- journal article
- research article
- Published by Wiley in Protein Science
- Vol. 21 (12), 1849-1857
- https://doi.org/10.1002/pro.2166
Abstract
Integrase is the key enzyme that mediates integration of retroviral DNA into cellular DNA which is essential for viral replication. Inhibitors of HIV‐1 that target integrase recognize the nucleoprotein complexes formed by integrase and viral DNA substrate (intasomes) rather than the free enzyme. Atomic resolution structures of HIV‐1 intasomes are therefore required to understand the mechanisms of inhibition and drug resistance. To date, prototype foamy virus (PFV) is the only retrovirus for which such structures have been determined. We show that PFV strand transfer complexes (STC) can be assembled on product DNA without going through the normal forward reaction pathway. The finding that a retroviral STC can be assembled in this way may provide a powerful tool to alleviate the obstacles that impede structural studies of nucleoprotein intermediates in HIV‐1 DNA integration.Keywords
Funding Information
- Intramural Program of NIDDK
- NIH
- AIDS Targeted Antiviral Program of the Office of the Director of the NIH
This publication has 19 references indexed in Scilit:
- DNA requirements for assembly and stability of HIV-1 intasomesProtein Science, 2012
- The mechanism of retroviral integration from X-ray structures of its key intermediatesNature, 2010
- Structure-based modeling of the functional HIV-1 intasome and its inhibitionProceedings of the National Academy of Sciences, 2010
- Retroviral intasome assembly and inhibition of DNA strand transferNature, 2010
- PHENIX: a comprehensive Python-based system for macromolecular structure solutionActa Crystallographica Section D-Biological Crystallography, 2010
- Functional and structural characterization of the integrase from the prototype foamy virusNucleic Acids Research, 2008
- Control of transposase activity within a transpososome by the configuration of the flanking DNA segment of the transposonProceedings of the National Academy of Sciences, 2007
- Coot: model-building tools for molecular graphicsActa Crystallographica Section D-Biological Crystallography, 2004
- [20] Processing of X-ray diffraction data collected in oscillation modeMethods in Enzymology, 1997
- A nucleoprotein complex mediates the integration of retroviral DNA.Genes & Development, 1989