Visualizing transient events in amino-terminal autoprocessing of HIV-1 protease

HIV-1 protease unmasked The HIV-1 protease enzyme is indispensable for viral maturation, making it a major potential target of anti-HIV therapy. Its role is to split newly formed Gag and Gag-Pol polyproteins to produced finished structural and functional proteins — itself included. The early events in the autoprocessing of HIV-1 protease, in which a precursor dimer is thought to undergo intramolecular cleavage, have now been visualized using NMR spectroscopy and paramagnetic relaxation enhancement. This reveals that although primarily monomeric, the protease is also present as transient encounter complexes that occupy a wide range of orientations relative to the mature dimer. The N-terminal region makes transient intra- and intersubunit contacts with the substrate binding site, allowing autocleavage to occur when the correct dimer orientation is sampled by the encounter complex.