Crystal structure of an RNA·DNA hybrid reveals intermolecular intercalation: Dimer formation by base-pair swapping

AUTOR(ES)

Han, Gye Won

FONTE

National Academy of Sciences

RESUMO

An intermolecular intercalation of base pairs was found at the CA step in the I222 crystal structure of the RNA·DNA hybrid, r(CAAAGAAAAG)·d(CTTTTCTTTG), which contains two-thirds of the polypurine tract sequence of HIV-1 with a substitution of cytosine for the initial adenine. This sequence crystallized in both P212121 and I222 space groups, with an rms difference of only 0.63 Å between residues 3 to 18 of the two forms. P212121 and I222 helices are both A-like, but intercalation occurs only in the I222 crystal form. The present structure shows bases stacked in parallel rather than perpendicular as in intercalated DNA (I-DNA). The base intercalation is also different from zipper-like meshing of bases seen in the center of the crystal structure of d(GCGAAAGCT), which does not have Watson–Crick base pairing. The base-step intercalation seen here is reminiscent of domain swapping in proteins; therefore, we call this phenomenon “base-pair swapping.” It involves a highly mobile CA step and seems to be sequence-specific and electrostatically stable without disrupting Watson–Crick interactions. It also exhibits a large rise concurrent with unwinding of the helix (low twist). We present a base-pair swapping dimer in nucleic acids.

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