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Structure of an RNA/DNA dodecamer corresponding to the HIV‐1 polypurine tract at 1.6 Å resolution

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The crystal structure of an RNA/DNA hybrid dodecamer, r(5′‐uaaaagaaaagg):d(5′‐CCTTTTCTTTTA), which contains three‐quarters of the polypurine tract (PPT) sequence of the HIV RNA genome is reported. The hybrid structure was determined at 1.6 Å resolution and was found to have the A‐form conformation. However, the presence of alternate conformations along the RNA template strand indicated increased flexibility of the PPT sequence. Two segments (at nucleotides 1–2 and 6–8) of the RNA chain have two conformations exhibiting differences in torsion and pseudorotation angles. For conformation I(1–2, 6–8), 25% of the RNA sugars have the C2′‐exo pucker and the rest have the expected C3′‐endo pucker. The II1–2 and II6–8 conformations of the RNA strand have one sugar with the C2′‐exo pucker. None of the ribose rings exist in the C2′‐endo form, in contrast to a previous report which postulated a C2′‐endo ribose as a key structural element of the PPT. The widths of the minor groove for conformations I(1–2, 6–8) and II(1–2, 6–8) of the RNA strand are 9.2–10.5 and 9.4–10.7 Å, respectively. Both ranges are very close to the intervals accepted for A‐form RNA duplexes. On the opposing DNA primer strand most of the sugars are C3′‐endo, except for the 3′‐terminal sugars, which are C2′‐endo (T22) or O4′‐endo (T23 and A24). The duplex includes a noncanonical u1(anti)·A24(syn) base interaction with only one hydrogen bond between the bases. This noncanonical base interaction at the 5′‐end of the template distorts the values of the helical parameters of the adjacent base pair.

Document Type: Research Article


Publication date: February 1, 2012


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