Nucleic Acids Research, Vol 24, Issue 20 3974-3981, Copyright © 1996 by Oxford University Press
F Aboul-ela, J Karn and G Varani
Efficient transcription from the human immunodeficiency virus (HIV)
promoter depends on binding of the viral regulatory protein Tat to a
cis-acting RNA regulatory element, TAR. Tat binds at a trinucleotide bulge
located near the apex of the TAR stem-loop structure. An essential feature
of Tat-TAR interaction is that the protein induces a conformational change
in TAR that repositions the functional groups on the bases and the
phosphate backbone that are critical for specific intermolecular
recognition of TAR RNA. We have previously determined a high resolution
structure for the bound form of TAR RNA using heteronuclear NMR. Here, we
describe a high resolution structure of the free TAR RNA based on 871
experimentally determined restraints. In the free TAR RNA, bulged residues
U23 and C24 are stacked within the helix, while U25 is looped out. This
creates a major distortion of the phosphate backbone between C24 and G26.
In contrast, in the bound TAR RNA, each of the three residues from the
bulge are looped out of the helix and U23 is drawn into proximity with G26
through contacts with an arginine residue that is inserted between the two
bases. Thus, TAR RNA undergoes a transition from a structure with an open
and accessible major groove to a much more tightly packed structure that is
folded around basic side chains emanating from the Tat protein.
ARTICLES
Structure of HIV-1 TAR RNA in the absence of ligands reveals a novel conformation of the trinucleotide bulge
MRC Laboratory of Molecular Biology, Cambridge, UK.
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