3mi9

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[[Image:3mi9.png|left|200px]]
 
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{{STRUCTURE_3mi9| PDB=3mi9 | SCENE= }}
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==Crystal structure of HIV-1 Tat complexed with human P-TEFb==
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<StructureSection load='3mi9' size='340' side='right'caption='[[3mi9]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3mi9]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/HIV-1_M:B_HXB2R HIV-1 M:B_HXB2R] 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=3MI9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3MI9 FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3mi9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3mi9 OCA], [https://pdbe.org/3mi9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3mi9 RCSB], [https://www.ebi.ac.uk/pdbsum/3mi9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3mi9 ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/CDK9_HUMAN CDK9_HUMAN] Note=Chronic activation of CDK9 causes cardiac myocyte enlargement leading to cardiac hypertrophy, and confers predisposition to heart failure.
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== Function ==
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[https://www.uniprot.org/uniprot/CDK9_HUMAN CDK9_HUMAN] Protein kinase involved in the regulation of transcription. Member of the cyclin-dependent kinase pair (CDK9/cyclin-T) complex, also called positive transcription elongation factor b (P-TEFb), which facilitates the transition from abortive to productive elongation by phosphorylating the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAP II) POLR2A, SUPT5H and RDBP. This complex is inactive when in the 7SK snRNP complex form. Phosphorylates EP300, MYOD1, RPB1/POLR2A and AR, and the negative elongation factors DSIF and NELF. Regulates cytokine inducible transcription networks by facilitating promoter recognition of target transcription factors (e.g. TNF-inducible RELA/p65 activation and IL-6-inducible STAT3 signaling). Promotes RNA synthesis in genetic programs for cell growth, differentiation and viral pathogenesis. P-TEFb is also involved in cotranscriptional histone modification, mRNA processing and mRNA export. Modulates a complex network of chromatin modifications including histone H2B monoubiquitination (H2Bub1), H3 lysine 4 trimethylation (H3K4me3) and H3K36me3; integrates phosphorylation during transcription with chromatin modifications to control co-transcriptional histone mRNA processing. The CDK9/cyclin-K complex has also a kinase activity towards CTD of RNAP II and can substitute for CDK9/cyclin-T P-TEFb in vitro. Replication stress response protein; the CDK9/cyclin-K complex is required for genome integrity maintenance, by promoting cell cycle recovery from replication arrest and limiting single-stranded DNA amount in response to replication stress, thus reducing the breakdown of stalled replication forks and avoiding DNA damage. In addition, probable function in DNA repair of isoform 2 via interaction with KU70/XRCC6. Promotes cardiac myocyte enlargement. RPB1/POLR2A phosphorylation on 'Ser-2' in CTD activates transcription. AR phosphorylation modulates AR transcription factor promoter selectivity and cell growth. DSIF and NELF phosphorylation promotes transcription by inhibiting their negative effect. The phosphorylation of MYOD1 enhances its transcriptional activity and thus promotes muscle differentiation.<ref>PMID:9857195</ref> <ref>PMID:10393184</ref> <ref>PMID:10574912</ref> <ref>PMID:10912001</ref> <ref>PMID:10757782</ref> <ref>PMID:11145967</ref> <ref>PMID:11112772</ref> <ref>PMID:11575923</ref> <ref>PMID:11884399</ref> <ref>PMID:11809800</ref> <ref>PMID:12037670</ref> <ref>PMID:15564463</ref> <ref>PMID:14701750</ref> <ref>PMID:17956865</ref> <ref>PMID:18362169</ref> <ref>PMID:19844166</ref> <ref>PMID:19575011</ref> <ref>PMID:20493174</ref> <ref>PMID:20930849</ref> <ref>PMID:20081228</ref> <ref>PMID:20980437</ref> <ref>PMID:21127351</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/mi/3mi9_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=3mi9 ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Regulation of the expression of the human immunodeficiency virus (HIV) genome is accomplished in large part by controlling transcription elongation. The viral protein Tat hijacks the host cell's RNA polymerase II elongation control machinery through interaction with the positive transcription elongation factor, P-TEFb, and directs the factor to promote productive elongation of HIV mRNA. Here we describe the crystal structure of the Tat.P-TEFb complex containing HIV-1 Tat, human Cdk9 (also known as CDK9), and human cyclin T1 (also known as CCNT1). Tat adopts a structure complementary to the surface of P-TEFb and makes extensive contacts, mainly with the cyclin T1 subunit of P-TEFb, but also with the T-loop of the Cdk9 subunit. The structure provides a plausible explanation for the tolerance of Tat to sequence variations at certain sites. Importantly, Tat induces significant conformational changes in P-TEFb. This finding lays a foundation for the design of compounds that would specifically inhibit the Tat.P-TEFb complex and block HIV replication.
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===Crystal structure of HIV-1 Tat complexed with human P-TEFb===
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Crystal structure of HIV-1 Tat complexed with human P-TEFb.,Tahirov TH, Babayeva ND, Varzavand K, Cooper JJ, Sedore SC, Price DH Nature. 2010 Jun 10;465(7299):747-51. PMID:20535204<ref>PMID:20535204</ref>
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{{ABSTRACT_PUBMED_20535204}}
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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==About this Structure==
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<div class="pdbe-citations 3mi9" style="background-color:#fffaf0;"></div>
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[[3mi9]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3MI9 OCA].
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==See Also==
==See Also==
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*[[Cyclin|Cyclin]]
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*[[Cyclin 3D structures|Cyclin 3D structures]]
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*[[Cyclin-dependent kinase 3D structures|Cyclin-dependent kinase 3D structures]]
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==Reference==
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*[[Tat protein|Tat protein]]
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<ref group="xtra">PMID:020535204</ref><references group="xtra"/>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: HIV-1 M:B_HXB2R]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Human immunodeficiency virus 1]]
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[[Category: Large Structures]]
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[[Category: Babayeva, N D.]]
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[[Category: Babayeva ND]]
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[[Category: Cooper, J J.]]
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[[Category: Cooper JJ]]
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[[Category: Price, D H.]]
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[[Category: Price DH]]
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[[Category: Sedore, S C.]]
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[[Category: Sedore SC]]
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[[Category: Tahirov, T H.]]
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[[Category: Tahirov TH]]
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[[Category: Varzavand, K.]]
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[[Category: Varzavand K]]
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[[Category: Hiv-1]]
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[[Category: P-tefb]]
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[[Category: Protein binding]]
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[[Category: Tat]]
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Current revision

Crystal structure of HIV-1 Tat complexed with human P-TEFb

PDB ID 3mi9

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