HIV-1 protease processes the Gag and Gag-Pol polyproteins into mature structural and functional proteins. The mature protease is only active as a dimer, with catalytic residues contributed by each subunit. The precursor of the active protease undergoes 'maturation' via the intramolecular cleavage of a dimeric species, but it is not clear how this cleavage reaction occurs. The early events in N-terminal auto-processing were visualized using NMR spectroscopy, and it was determined that the precursor forms transient, lowly populated dimeric 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, enabling auto-cleavage to occur when the correct dimer orientation is sampled by the encounter complex ensemble.
- Chun Tang
- John M. Louis
- G. Marius Clore
