2b8r

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Template:STRUCTURE 2b8r

Structure oF HIV-1(LAI) genomic RNA DIS

Overview

We describe the crystal structures of the RNA dimerization initiation sites (DIS) of HIV-1 subtypes A and B. Both molecules adopt a hairpin conformation, with loop sequences consisting of 272-AGGUGCACA-280 and 272-AAGCGCGCA-280, respectively. This includes a six-base self-complementary stretch (underlined) that allows homodimerization through the formation of a loop-loop, or 'kissing-loop', complex. The DISs for the two sequences have identical conformations, and the two interacting hairpins show a perfect coaxial alignment. The conserved purines, A272 and R273, are stacked in a bulged-out conformation and symmetrically join the upward and downward strands of each hairpin by crossing the helix major groove. There is good agreement between these structures and previous results from chemical probing in solution, as well as with differences in magnesium dependence for dimerization. The overall shape of the kissing-loop complex is very similar to that of the previously determined subtype A DIS duplex form. Unexpectedly, the purine R273 is the only base seen at a different position and is responsible for the difference in topology between the two forms. We propose that the transition from kissing-loop duplex could occur by a recombination mechanism based on symmetrical chain cleavage at R273 of each hairpin and subsequent cross-religation, rather than by base-pair melting and subsequent reannealing.

About this Structure

This structure supersedes the now removed PDB entry 1jjm. Full crystallographic information is available from OCA.

Reference

Crystal structures of coaxially stacked kissing complexes of the HIV-1 RNA dimerization initiation site., Ennifar E, Walter P, Ehresmann B, Ehresmann C, Dumas P, Nat Struct Biol. 2001 Dec;8(12):1064-8. PMID:11702070 Page seeded by OCA on Sat May 3 19:59:29 2008