Crystal structure of HIV-1 reverse transcriptase in complex with a polypurine tract RNA : DNA

We have determined the 3.0 Angstrom resolution structure of wild-type HIV-1 reverse transcriptase in complex with an RNA:DNA oligonucleotide whose seq uence includes a purine-rich segment from the HIV-1 genome called the polyp urine tract (PPT). The PPT is resistant to ribonuclease H (RNase H) cleavag e and is used as a primer for second DNA strand synthesis. The 'RNase H pri mer grip', consisting of amino acids that interact with the DNA primer stra nd, may contribute to PNase H catalysis and cleavage specificity. Cleavage specificity is also controlled by the width of the minor groove and the tra jectory of the RNA:DNA, both of which are sequence dependent, An unusual 'u nzipping' of 7 bp occurs in the adenine stretch of the PPT: an unpaired bas e on the template strand takes the base pairing out of register and then, f ollowing two offset base pairs, an unpaired base on the primer strand re-es tablishes the normal register. The structural aberration extends to the RNa se H active site and may play a role in the resistance of PPT to RNase H cl eavage.