Figure 1.   The structure of the RT/RNA/DNA complex.  (A) The figure shows a ribbon diagram of RT.  p51 is gray, the fingers of p66 are blue, the palm is red, the thumb is green, the connection is yellow, and RNase H is orange.  The DNA (primer) strand is pink; the RNA (template) strand is blue.  Overall, the structure is similar to a complex in which the bound nucleic acid is a DNA/DNA duplex despite the fact that nucleic acid sequences in the RNA/DNA and DNA/DNA complexes are quite different.  In both complexes, the nucleic acids are bent; the bend is near the thumb of p66.  However, a closer examination of the structure of the RNA/DNA duplex shows the region that contains two mispaired bases flanked by two unpaired bases; these serve to bring the pairing out of and then back into register.  Because this mispairing is so unusual, it is possible that it plays an important role in determining the specificity of RNase H cleavage.  (B) Diagram of the nucleic acid in the RNA/DNA duplex bound to HIV-1 RT.  The diagram shows the two unpaired bases: A869 in the RNA strand (lower strand shown in green), and C883 in the DNA strand (upper strand shown in pink).  The mispaired bases, an A·T and a G·T, lie between the unpaired bases.  The diagram also shows the scissile phosphate (red arrow) and the amino acids that contact the nucleic acid.  The "RNase H primer grip" is a group of amino acids in the connection subdomain and the RNase H domain that contact the DNA strand 3' (on the DNA) of the scissile phosphate.