FIGURE 2. The dual binding mode of HIV reverse transcriptase.

As part of the virus's RNA genome, the PPT sequence acts as a template for the synthesis of the minus-strand DNA. a, Abbondanzieri et al.¹ show that, before cleavage of the PPT RNA, HIV reverse transcriptase binds to PPT (blue sequence) in an RNase H mode — that is, the RNase H domain of the enzyme is close to the 3 end of PPT (circled), thus blocking the polymerase domain's access to it and preventing premature extension. b, When the RNA nucleotides next to the PPT sequence are cleaved, allowing PPT to function as a primer, the enzyme can bind in a polymerase-competent mode (with its polymerase domain close to PPT's 3 end) to initiate DNA synthesis. The HIV reverse transcriptase seems to rapidly switch orientation between these two binding modes.