A single deletion at position 134, 135, or 136 in the beta 7-beta 8 loop of the p51 subunit of HIV-1 RT disrupts the formation of heterodimeric enzyme

The human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) is a heterodimeric enzyme composed of p66 and p51 subunits. Earlier, we showed that the β7-β8 loop of p51 is crucial for polymerase activity of HIV-1 RT as either deletion or Ala substitution of amino acids in the β7-β8 loop spanning residues 136-139 in the p51 subunit impaired dimerization and, in turn, polymerase function of the enzyme (Pandey et al. [2001] Biochemistry 40: 9505-9512). In the present study, we generated subunit-specific single-deletion mutants at positions 134, 135, 136, or 137 and examined their effects on the heterodimerization, binary complex formation, and polymerase functions of the enzyme. We found that among these four residues, Ser134, Ile135, and Asn136 in the β7-β8 loop of the p51 subunit are crucial residues for dimerization and polymerase function of the enzyme, but have no impact when specifically deleted from the p66 subunit. These results demonstrate the β7-β8 loop of the p51 subunit in the formation of stable, functional heterodimeric enzyme which could be an attractive target for anti-HIV-1 drug development.