Molecular recognition in the bovine immunodeficiency virus Tat peptide-TAR RNA complex Journal Article
| Authors: | Ye, X.; Kumar, R. A.; Patel, D. J. |
| Article Title: | Molecular recognition in the bovine immunodeficiency virus Tat peptide-TAR RNA complex |
| Abstract: | 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 (3-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 ∼40° 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 β-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. © 1995. |
| Keywords: | animal; animals; animalia; chemistry; virus rna; transactivator protein; lentivirus; hydrogen bond; hydrogen bonding; protons; isoleucine; cattle; human immunodeficiency virus; conformation; nucleic acid conformation; nuclear magnetic resonance; glycine; rna, viral; proton; nuclear magnetic resonance, biomolecular; bovinae; bos taurus; humans; human; article; gene products, tat; bovine immunodeficiency like virus; immunodeficiency virus, bovine; bovine immunodeficiency virus; bovine immunodeficiency-like virus; arginine-guanine interactions; buttressing u·au base triple; glycine and isoleucine packing; peptide-rna recognition; rna bending |
| Journal Title: | Chemistry and Biology |
| Volume: | 2 |
| Issue: | 12 |
| ISSN: | 1074-5521 |
| Publisher: | Elsevier Inc. |
| Date Published: | 1995-12-01 |
| Start Page: | 827 |
| End Page: | 840 |
| Language: | English |
| DOI: | 10.1016/1074-5521(95)90089-6 |
| PUBMED: | 8807816 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 28 August 2018 -- Source: Scopus |
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