NMR structure of the mature dimer initiation complex of HIV-1 genomic RNA.

The two identical genomic RNA strands inside each HIV-1 viral particle are linked through homodimerization of an RNA stem-loop, termed SL1, near their 5' ends. SL1 first dimerizes through a palindromic sequence in its loop, forming a transient kissing-loop complex which then refolds to a mature, linear duplex. We previously reported the NMR structure of a 23-base truncate of SLI in kissing-dimer form, and here report the high-resolution structure of its linear isoform. This structure comprises three short duplex regions--derived from the central palindrome and two stem regions of each strand, respectively--separated by two bulges that each encompass three unpaired adenines flanking the palindromes. The stacking pattern of these adenines differs from that seen in the kissing-loop complex, and leads to greater colinear base stacking overall. Moreover, the mechanical distortion of the palindrome helix is reduced, and base pairs ruptured during formation of the kissing-loop complex are re-established, so that all potential Watson-Crick pairs are intact. These features together likely account for the greater thermodynamic stability of the mature dimer as compared to its kissing-loop precursor.