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[[Image:2pk2.jpg|left|200px]]


{{Structure
==Cyclin box structure of the P-TEFb subunit Cyclin T1 derived from a fusion complex with EIAV Tat==
|PDB= 2pk2 |SIZE=350|CAPTION= <scene name='initialview01'>2pk2</scene>, resolution 2.67&Aring;
<StructureSection load='2pk2' size='340' side='right'caption='[[2pk2]], [[Resolution|resolution]] 2.67&Aring;' scene=''>
|SITE=  
== Structural highlights ==
|LIGAND=  
<table><tr><td colspan='2'>[[2pk2]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Equine_infectious_anemia_virus Equine infectious anemia virus] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PK2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2PK2 FirstGlance]. <br>
|ACTIVITY=  
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.67&#8491;</td></tr>
|GENE=  
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2pk2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pk2 OCA], [https://pdbe.org/2pk2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2pk2 RCSB], [https://www.ebi.ac.uk/pdbsum/2pk2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2pk2 ProSAT]</span></td></tr>
|DOMAIN=
</table>
|RELATEDENTRY=[[1pkw|1PKW]]
== Function ==
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2pk2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pk2 OCA], [http://www.ebi.ac.uk/pdbsum/2pk2 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2pk2 RCSB]</span>
[https://www.uniprot.org/uniprot/TAT_EIAVC TAT_EIAVC] 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 enhance transcription by the RNA polymerase II (RNA pol II) complex, thereby increasing the level of full-length transcripts. Tat associates with the CCNT1/cyclin-T1 component of the P-TEFb complex (CDK9 and CCNT1), which promotes RNA chain elongation. This binding increases Tat's affinity for a branched hairpin structure at the 5'-end of all nascent viral mRNAs referred to as the transactivation responsive RNA element (TAR RNA). The CDK9 component of P-TEFb hyperphosphorylates the C-terminus of RNA Pol II that becomes stabilized and much more processive (By similarity).[https://www.uniprot.org/uniprot/CCNT1_HUMAN CCNT1_HUMAN] Regulatory subunit of the cyclin-dependent kinase pair (CDK9/cyclin-T1) complex, also called positive transcription elongation factor B (P-TEFb), which is proposed to facilitate the transition from abortive to productive elongation by phosphorylating the CTD (carboxy-terminal domain) of the large subunit of RNA polymerase II (RNA Pol II). In case of HIV or SIV infections, binds to the transactivation domain of the viral nuclear transcriptional activator, Tat, thereby increasing Tat's affinity for the transactivating response RNA element (TAR RNA). Serves as an essential cofactor for Tat, by promoting RNA Pol II activation, allowing transcription of viral genes.
}}
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/pk/2pk2_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2pk2 ConSurf].
<div style="clear:both"></div>


'''Cyclin box structure of the P-TEFb subunit Cyclin T1 derived from a fusion complex with EIAV Tat'''
==See Also==
 
*[[Tat protein|Tat protein]]
 
__TOC__
==Overview==
</StructureSection>
The positive transcription elongation factor b (P-TEFb) is an essential regulator of viral gene expression during the life cycle of human immunodeficiency virus type 1 (HIV-1). Its cyclin T1 subunit forms a ternary complex with the viral transcriptional transactivator (Tat) protein and the transactivation response (TAR) RNA element thereby activating cyclin dependent kinase 9 (Cdk9), which stimulates transcription at the level of chain elongation. We report the structure of the cyclin box domain of human cyclin T1 at a resolution of 2.67 A. The structure was obtained by crystallographic analysis of a fusion protein composed of cyclin T1 linked to the transactivator protein Tat from equine infectious anemia virus (EIAV), which is functionally and structurally related to HIV-1 Tat. The conserved cyclin box domain of cyclin T1 exhibits structural features for interaction with physiological binding partners such as Cdk9. A recognition site for Cdk/Cyclin substrates is partly covered by a cyclin T-specific insert, suggesting specific interactions with regulatory factors. The previously identified Tat/TAR recognition motif (TRM) forms a C-terminal helix that is partly occluded in the cyclin box repeat interface, while cysteine 261 is accessible to form an intermolecular zinc finger with Tat. Residues of the TRM contribute to a positively charged groove that may directly attract RNA molecules. The EIAV Tat protein instead appeared undefined from the electron density map suggesting that it is highly disordered. Functional experiments confirmed the TAR binding properties of the fusion protein and suggested residues on the second cyclin box repeat to contribute to Tat stimulated transcription.
[[Category: Equine infectious anemia virus]]
 
[[Category: Homo sapiens]]
==About this Structure==
[[Category: Large Structures]]
2PK2 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens,_equine_infectious_anemia_virus Homo sapiens, equine infectious anemia virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PK2 OCA].
[[Category: Anand K]]
 
[[Category: Fujinaga K]]
==Reference==
[[Category: Geyer M]]
Cyclin box structure of the P-TEFb subunit cyclin T1 derived from a fusion complex with EIAV tat., Anand K, Schulte A, Fujinaga K, Scheffzek K, Geyer M, J Mol Biol. 2007 Jul 27;370(5):826-36. Epub 2007 May 10. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17540406 17540406]
[[Category: Scheffzek K]]
[[Category: Homo sapiens, equine infectious anemia virus]]
[[Category: Schulte A]]
[[Category: Single protein]]
[[Category: Anand, K.]]
[[Category: Fujinaga, K.]]
[[Category: Geyer, M.]]
[[Category: Scheffzek, K.]]
[[Category: Schulte, A.]]
[[Category: cyclin t1]]
[[Category: tar]]
[[Category: tat]]
[[Category: transcription regulation p-tefb]]
[[Category: twinning]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:37:00 2008''

Latest revision as of 12:10, 21 February 2024

Cyclin box structure of the P-TEFb subunit Cyclin T1 derived from a fusion complex with EIAV TatCyclin box structure of the P-TEFb subunit Cyclin T1 derived from a fusion complex with EIAV Tat

Structural highlights

2pk2 is a 4 chain structure with sequence from Equine infectious anemia virus and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.67Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

TAT_EIAVC 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 enhance transcription by the RNA polymerase II (RNA pol II) complex, thereby increasing the level of full-length transcripts. Tat associates with the CCNT1/cyclin-T1 component of the P-TEFb complex (CDK9 and CCNT1), which promotes RNA chain elongation. This binding increases Tat's affinity for a branched hairpin structure at the 5'-end of all nascent viral mRNAs referred to as the transactivation responsive RNA element (TAR RNA). The CDK9 component of P-TEFb hyperphosphorylates the C-terminus of RNA Pol II that becomes stabilized and much more processive (By similarity).CCNT1_HUMAN Regulatory subunit of the cyclin-dependent kinase pair (CDK9/cyclin-T1) complex, also called positive transcription elongation factor B (P-TEFb), which is proposed to facilitate the transition from abortive to productive elongation by phosphorylating the CTD (carboxy-terminal domain) of the large subunit of RNA polymerase II (RNA Pol II). In case of HIV or SIV infections, binds to the transactivation domain of the viral nuclear transcriptional activator, Tat, thereby increasing Tat's affinity for the transactivating response RNA element (TAR RNA). Serves as an essential cofactor for Tat, by promoting RNA Pol II activation, allowing transcription of viral genes.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

2pk2, resolution 2.67Å

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