Initiation of HIV reverse transcription: is enzyme flipping required?

Liu and colleagues have recently studied dynamic changes in the orientation of HIV reverse transcriptase (RT) on its nucleic acid substrate during initiation of DNA synthesis. The authors employed a single molecule FRET assay and revealed the existence of an equilibrium between polymerase-competent and "flipped" polymerase-incompetent orientations. RT flipping correlates with enzyme pausing during initiation, while the transition to the processive elongation phase correlates with increases in the population of polymerase-competent complexes. The potential biological significance of these findings is discussed in this commentary in lieu of the entire process of reverse transcription.