A Synthetic Peptide from the Human Immunodeficiency Virus Type-1 Integrase Exhibits Coiled-Coil Properties and Interferes with the in Vitro Integration Activity of The Enzyme

Correlated Biochemical and Spectroscopic Results


S. Fermandjian, Département de Biologie structurale, CNRS URA 147, Institut Gustave Roussy, PR2, 39 rue Camille Desmoulins, F-94805 Villejuif, France
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Integration of the human immunodeficiency virus (HIV-1) DNA into the host genome is catalysed by a virus-encoded protein integrase. Here, we report some of the structural and functional properties of two synthetic peptides: integrase-(147–175)-peptide reproducing the residues 147–175 (SQGVVESMNKELK159KIIGQVRDQAEHLKTAY) of the HIV-1 integrase, and [Pro159] integrase-(147–175)-peptide where the lysine 159 is substituted for a proline. Circular dichroism revealed that both peptides are mostly under unordered conformation in aqueous solution, contrasting with the α-helix exhibited by residues 147–175 in the protein crystal structure. In a weak α-helix-promoting environment, integrase-(147–175)-peptide self-associated into stable coiled-coil oligomers, while [Pro159] integrase-(147–175)-peptide did not. This property was further confirmed by cross-linking experiments. In our in vitro experiments, 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 structure disturbing the catalytic properties of the enzyme.


avian sarcoma virus


human immunodeficiency virus


long terminal repeat


eletrospray-ionisatiou mass spectrometry