A SYNTHETIC PEPTIDE FROM THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INTEGRASE EXHIBITS COILED-COIL PROPERTIES AND INTERFERES WITH THE IN-VITROINTEGRATION ACTIVITY OF THE ENZYME - CORRELATED BIOCHEMICAL AND SPECTROSCOPIC RESULTS

Integration of the human immunodeficiency virus (HIV-1) DNA into the h ost genome is catalysed by a virus-encoded protein integrase. Here, we report some of the structural and functional properties of two synthe tic peptides: integrase-(147-175)-peptide reproducing the residues 147 -175 (SQGVVESMN-KELK159KIIGQVRDQAEHLKAY) of the HIV-1 integrase, and [ Pro159] integrase-(147-175)-peptide where the lysine 159 is substitute d for a proline. Circular dichroism revealed that both peptides are mo stly under unordered conformation in aqueous solution, contrasting wit h the alpha-helix exhibited by residues 147-175 in the protein crystal structure, In a weak alpha-helix-promoting environment, integrase-(14 7-175)-peptide self-associated into stable coiled-coil oligomers, whil e [Pro159] integrase-(147-175)-peptide did not. This property was furt her confirmed by cross-linking experiments. In our in vitro experiment s, only integrase-(147-175)-peptide was able to reduce the integration activity of the enzyme. We propose that the inhibitory activity shown by integrase-(147-175)-peptide is dependent on its ability to bind to its counterpart in integrase through a peptide-protein coiled-coil st ructure disturbing the catalytic properties of the enzyme.