1biv
From Proteopedia
(New page: 200px<br /><applet load="1biv" size="450" color="white" frame="true" align="right" spinBox="true" caption="1biv" /> '''BOVINE IMMUNODEFICIENCY VIRUS TAT-TAR COMPLE...) |
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| - | [[Image:1biv.gif|left|200px]]<br /><applet load="1biv" size=" | + | [[Image:1biv.gif|left|200px]]<br /><applet load="1biv" size="350" color="white" frame="true" align="right" spinBox="true" |
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'''BOVINE IMMUNODEFICIENCY VIRUS TAT-TAR COMPLEX, NMR, 5 STRUCTURES'''<br /> | '''BOVINE IMMUNODEFICIENCY VIRUS TAT-TAR COMPLEX, NMR, 5 STRUCTURES'''<br /> | ||
==Overview== | ==Overview== | ||
| - | BACKGROUND: In lentiviruses such as human immunodeficiency virus (HIV) and | + | 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. |
==About this Structure== | ==About this Structure== | ||
| - | 1BIV is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bovine_immunodeficiency_virus Bovine immunodeficiency virus]. Full crystallographic information is available from [http:// | + | 1BIV is a [http://en.wikipedia.org/wiki/Single_protein 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]. |
==Reference== | ==Reference== | ||
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[[Category: Bovine immunodeficiency virus]] | [[Category: Bovine immunodeficiency virus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Kumar, R | + | [[Category: Kumar, R A.]] |
| - | [[Category: Patel, D | + | [[Category: Patel, D J.]] |
[[Category: Ye, X.]] | [[Category: Ye, X.]] | ||
[[Category: arg-gua interactions]] | [[Category: arg-gua interactions]] | ||
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[[Category: tat-tar]] | [[Category: tat-tar]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:55:51 2008'' |
Revision as of 09:55, 21 February 2008
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BOVINE IMMUNODEFICIENCY VIRUS TAT-TAR COMPLEX, NMR, 5 STRUCTURES
Overview
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.
About this Structure
1BIV is a Single protein structure of sequence from Bovine immunodeficiency virus. Full crystallographic information is available from OCA.
Reference
Molecular recognition in the bovine immunodeficiency virus Tat peptide-TAR RNA complex., Ye X, Kumar RA, Patel DJ, Chem Biol. 1995 Dec;2(12):827-40. PMID:8807816
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