Every machine is made of parts. But, as the new structure of the HIV integrase enzyme in complex with viral DNA shows, one could not have predicted from the individual parts just how this machine works.Retroviruses such as human immunodeficiency virus type 1 (HIV-1) integrate a DNA copy of their genome into their host genome as an obligatory step in their replication cycle. The DNA cutting-and-pasting reactions that lead to integration are mediated by the virus's integrase enzyme. The structures of this enzyme's three domains - the core catalytic domain, the amino-terminal domain and the carboxy-terminal domain - have been solved previously. But the spatial organization of the domains with viral DNA when in the active nucleoprotein complex (known as the intasome), which carries out integration, has remained unknown. In this issue (page 232), Hare et aV describe the structure of a retroviral intasome. The structure clarifies many poorly understood aspects of retroviral-DNA integration. What's more, it provides a solid platform for understanding the mechanism by which the inhibitors of this essential viral enzyme act (Fig. 1).
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Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA;
