Structural biology: When four become one

Abstract

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.

Figure 1. The pieces of the intasome puzzle

An integrase monomer consists of three structural domains: the amino-terminal helical bundle, the core catalytic domain and the carboxy-terminal domain. Viral DNA integration into the host genome is, however, catalysed by a highly stable nucleoprotein complex called the intasome, in which four integrase monomers bridge a pair of viral DNA ends — a structure that Hare et al. have now solved, putting the pieces of the puzzle together. Inhibitors of HIV-1 integrase bind to the intasome rather than to free integrase, making the new structure particularly valuable.