BACKGROUND: In lentiviruses such as human immunodeficiency virus (HIV) and bovine immunodeficiency virus (BIV), the Tat (trans-activating) protein enhances transcription of the viral RNA by complexing to the 5'-end of the transcribed mRNA, at a region known as TAR (the trans-activation response element). Identification of the determinants that account for specific molecular recognition requires a high resolution structure of the Tat peptide-TAR RNA complex. RESULTS: We report here on the structural characterization of a complex of the recognition domains of BIV Tat and TAR in aqueous solution using a combination of NMR and molecular dynamics. The 17-mer Tat peptide recognition domain folds into a beta-hairpin and penetrates in an edge-on orientation deep into a widened major groove of the 28-mer TAR RNA recognition domain in the complex. The RNA fold is defined, in part, by two uracil bulged bases; U12 has a looped-out conformation that widens the major groove and U10 forms a U.AU base triple that buttresses the RNA helix. Together, these bulged bases induce a approximately 40 degree bend between the two helical stems of the TAR RNA in the complex. A set of specific intermolecular hydrogen bonds between arginine side chains and the major-groove edge of guanine residues contributes to sequence specificity. These peptide-RNA contacts are complemented by other intermolecular hydrogen bonds and intermolecular hydrophobic packing contacts involving glycine and isoleucine side chains. CONCLUSIONS: We have identified a new structural motif for protein-RNA recognition, a beta-hairpin peptide that interacts with the RNA major groove. Specificity is associated with formation of a novel RNA structural motif, a U.AU base triple, which facilitates hydrogen bonding of an arginine residue to a guanine and to a backbone phosphate. These results should facilitate the design of inhibitors that can disrupt HIV Tat-TAR association.
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==About this Structure==
==About this Structure==
1BIV is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Bovine_immunodeficiency_virus Bovine immunodeficiency virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BIV OCA].
1BIV is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Bovine_immunodeficiency_virus Bovine immunodeficiency virus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BIV OCA].
==Reference==
==Reference==
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[[Category: Rna bending]]
[[Category: Rna bending]]
[[Category: Tat-tar]]
[[Category: Tat-tar]]
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Revision as of 16:14, 30 June 2008
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