CONSERVED RESIDUES PRO-109 AND ASP-116 ARE REQUIRED FOR INTERACTION OF THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INTEGRASE PROTEIN WITH ITS VIRAL-DNA SUBSTRATE

The human immunodeficiency virus type 1 integrase protein can be speci fically cross-linked to viral long terminal repeat substrate oligonucl eotides in vitro by using UV light. Site-directed mutagenesis and dele tion analyses were used to define the domains involved in the interact ion of integrase with the viral DNA substrate. Our results showed that mutation of conserved residues Pro-109 and Asp-116, which are found t o be critical for the endonuclease and integration activities of IN pr otein, abolished the ability of the protein to cross-link to its DNA s ubstrate. Furthermore, deletion analysis experiments showed that remov al of 39 amino acids from the amino terminus and deletion of 15 amino acids from the carboxyl terminus abolished DNA cross-linking.