Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Protein Sci. 2012 Dec;21(12):1849-57. doi: 10.1002/pro.2166. Epub 2012 Oct 26.
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.
整合酶是介导逆转录病毒 DNA 整合到细胞 DNA 的关键酶，这对于病毒复制至关重要。靶向整合酶的 HIV-1 抑制剂识别由整合酶和病毒 DNA 底物（intasomes）形成的核蛋白复合物，而不是游离酶。因此，需要获得 HIV-1 整合酶核蛋白复合物的原子分辨率结构，以了解抑制和耐药机制。迄今为止，原型泡沫病毒 (PFV) 是唯一已确定此类结构的逆转录病毒。我们表明，PFV 链转移复合物 (STC) 可以在没有经过正常正向反应途径的情况下在产物 DNA 上组装。发现逆转录病毒 STC 可以以这种方式组装，可能为缓解阻碍 HIV-1 DNA 整合中核蛋白中间体结构研究的障碍提供了有力工具。
