Role of the nonspecific DNA-binding region and α helices within the core domain of retroviral integrase in selecting target DNA sites for integration

Retroviral integrase plays an import-ant role in choosing host chromosomal sites for integration of the cDNA copy of the viral genome. The domain responsible for target site selection has been previously mapped to the central core of the protein (amino acid residues 49-238). Chimeric integrases between human immunodeficiency virus type 1 (HIV-1) and feline immunodeficiency virus (FIV) were prepared to examine the involvement of a nonspecific DNA-binding region (residues 213-266) and certain a helices within the core domain in target site selection. Determination of the distribution and frequency of integration events of the chimeric integrases narrowed the target site-specifying motif to within residues 49-187 and showed that alpha3 and alpha4 helices (residues 123-166) were not involved in target site selection. Furthermore, the chimera with the alpha2 helix (residues 118-121) of FIV identity displayed characteristic integration events from both HIV-1 and FIV integrases. The results indicate that the alpha2 helix plays a role in target site preference as either part of a larger or multiple target site-specifying motif.