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| | ==BOVINE IMMUNODEFICIENCY VIRUS TAT-TAR COMPLEX, NMR, 5 STRUCTURES== | | ==BOVINE IMMUNODEFICIENCY VIRUS TAT-TAR COMPLEX, NMR, 5 STRUCTURES== |
| - | <StructureSection load='1biv' size='340' side='right'caption='[[1biv]], [[NMR_Ensembles_of_Models | 5 NMR models]]' scene=''> | + | <StructureSection load='1biv' size='340' side='right'caption='[[1biv]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1biv]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BIV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1BIV FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1biv]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bovine_immunodeficiency_virus Bovine immunodeficiency virus] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BIV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1BIV FirstGlance]. <br> |
| | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1biv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1biv OCA], [https://pdbe.org/1biv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1biv RCSB], [https://www.ebi.ac.uk/pdbsum/1biv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1biv ProSAT]</span></td></tr> | | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1biv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1biv OCA], [https://pdbe.org/1biv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1biv RCSB], [https://www.ebi.ac.uk/pdbsum/1biv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1biv ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/TAT_BIV29 TAT_BIV29]] Nuclear transcriptional activator of viral gene expression, that is essential for viral transcription from the LTR promoter and replication. Acts as a sequence-specific molecular adapter, directing components of the cellular transcription machinery to the viral RNA to promote processive transcription elongation by the RNA polymerase II (RNA pol II) complex, thereby increasing the level of full-length transcripts. Tat binds to a hairpin structure at the 5'-end of all nascent viral mRNAs referred to as the transactivation responsive RNA element (TAR RNA) in a CCNT1-independent mode. Tat then recruits the CCNT1/cyclin-T1 component of the P-TEFb complex (CDK9 and CCNT1), which promotes RNA chain elongation. The CDK9 component of P-TEFb hyperphosphorylates the C-terminus of RNA Pol II that becomes stabilized and much more processive (Probable).<ref>PMID:10846086</ref>
| + | [https://www.uniprot.org/uniprot/TAT_BIV29 TAT_BIV29] Nuclear transcriptional activator of viral gene expression, that is essential for viral transcription from the LTR promoter and replication. Acts as a sequence-specific molecular adapter, directing components of the cellular transcription machinery to the viral RNA to promote processive transcription elongation by the RNA polymerase II (RNA pol II) complex, thereby increasing the level of full-length transcripts. Tat binds to a hairpin structure at the 5'-end of all nascent viral mRNAs referred to as the transactivation responsive RNA element (TAR RNA) in a CCNT1-independent mode. Tat then recruits the CCNT1/cyclin-T1 component of the P-TEFb complex (CDK9 and CCNT1), which promotes RNA chain elongation. The CDK9 component of P-TEFb hyperphosphorylates the C-terminus of RNA Pol II that becomes stabilized and much more processive (Probable).<ref>PMID:10846086</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Bovine immunodeficiency virus]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Kumar, R A]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Patel, D J]] | + | [[Category: Kumar RA]] |
| - | [[Category: Ye, X]] | + | [[Category: Patel DJ]] |
| - | [[Category: Arg-gua interaction]] | + | [[Category: Ye X]] |
| - | [[Category: Glycine and isoleucine packing]]
| + | |
| - | [[Category: Peptide rna recognition]]
| + | |
| - | [[Category: Rna bending]]
| + | |
| - | [[Category: Tat-tar]]
| + | |
| - | [[Category: Viral protein-rna complex]]
| + | |
| Structural highlights
Function
TAT_BIV29 Nuclear transcriptional activator of viral gene expression, that is essential for viral transcription from the LTR promoter and replication. Acts as a sequence-specific molecular adapter, directing components of the cellular transcription machinery to the viral RNA to promote processive transcription elongation by the RNA polymerase II (RNA pol II) complex, thereby increasing the level of full-length transcripts. Tat binds to a hairpin structure at the 5'-end of all nascent viral mRNAs referred to as the transactivation responsive RNA element (TAR RNA) in a CCNT1-independent mode. Tat then recruits the CCNT1/cyclin-T1 component of the P-TEFb complex (CDK9 and CCNT1), which promotes RNA chain elongation. The CDK9 component of P-TEFb hyperphosphorylates the C-terminus of RNA Pol II that becomes stabilized and much more processive (Probable).[1]
Publication Abstract from PubMed
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.
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[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Barboric M, Taube R, Nekrep N, Fujinaga K, Peterlin BM. Binding of Tat to TAR and recruitment of positive transcription elongation factor b occur independently in bovine immunodeficiency virus. J Virol. 2000 Jul;74(13):6039-44. PMID:10846086
- ↑ Ye X, Kumar RA, Patel DJ. Molecular recognition in the bovine immunodeficiency virus Tat peptide-TAR RNA complex. Chem Biol. 1995 Dec;2(12):827-40. PMID:8807816
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