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.
Keywords: HIV; initiation; reverse transcription.