2b9d

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(New page: 200px<br /><applet load="2b9d" size="450" color="white" frame="true" align="right" spinBox="true" caption="2b9d, resolution 1.60&Aring;" /> '''Crystal Structure of...)
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[[Image:2b9d.gif|left|200px]]<br /><applet load="2b9d" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="2b9d, resolution 1.60&Aring;" />
 
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'''Crystal Structure of HPV E7 CR3 domain'''<br />
 
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==Overview==
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==Crystal Structure of HPV E7 CR3 domain==
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The E7 oncoprotein from human Papillomavirus (HPV) mediates cell, transformation in part by binding to the human pRb tumor suppressor, protein and E2F transcription factors, resulting in the dissociation of, pRb from E2F transcription factors and the premature cell progression into, the S-phase of the cell cycle. This activity is mediated by the LXCXE, motif and the CR3 zinc binding domain of the E7 protein. In this study we, report the x-ray crystal structure of the CR3 region of HPV E7 and a, structure-based mutational analysis to investigate its mode of pRb and E2F, binding and E2F displacement from pRb. The structure reveals a novel, zinc-bound E7-CR3 obligate homodimer that contains two surface patches of, sequence conservation. Mutation of residues within these patches reveals, that one patch is required for pRb binding, whereas the other is required, for E2F binding. We also show that both E7-mediated interactions are, required to disrupt pRb.E2F complexes. Based on these studies we present a, mechanistic model for how E7 displaces E2F from pRb. Because the CR3, region of HPV E7 has no detectable homology to other human proteins, the, structure-function studies presented here provide an avenue for developing, small molecule compounds that inhibit HPV-E7-mediated cell transformation.
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<StructureSection load='2b9d' size='340' side='right'caption='[[2b9d]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
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== Structural highlights ==
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==About this Structure==
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<table><tr><td colspan='2'>[[2b9d]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_papillomavirus_type_1a Human papillomavirus type 1a]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2B9D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2B9D FirstGlance]. <br>
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2B9D is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Human_papillomavirus_type_2a Human papillomavirus type 2a] with ZN as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2B9D OCA].
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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]] 1.6&#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=ZN:ZINC+ION'>ZN</scene></td></tr>
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==Reference==
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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=2b9d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2b9d OCA], [https://pdbe.org/2b9d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2b9d RCSB], [https://www.ebi.ac.uk/pdbsum/2b9d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2b9d ProSAT]</span></td></tr>
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Structure of the human Papillomavirus E7 oncoprotein and its mechanism for inactivation of the retinoblastoma tumor suppressor., Liu X, Clements A, Zhao K, Marmorstein R, J Biol Chem. 2006 Jan 6;281(1):578-86. Epub 2005 Oct 24. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16249186 16249186]
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</table>
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[[Category: Human papillomavirus type 2a]]
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== Function ==
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[[Category: Single protein]]
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[https://www.uniprot.org/uniprot/VE7_HPV1 VE7_HPV1] Plays a role in viral genome replication by driving entry of quiescent cells into the cell cycle. Stimulation of progression from G1 to S phase allows the virus to efficiently use the cellular DNA replicating machinery to achieve viral genome replication. E7 protein has both transforming and trans-activating activities. Induces the disassembly of the E2F1 transcription factor from RB1, with subsequent transcriptional activation of E2F1-regulated S-phase genes. Interferes with host histone deacetylation mediated by HDAC1 and HDAC2, leading to transcription activation. Also plays a role in the inhibition of both antiviral and antiproliferative functions of host interferon alpha. Interaction with host TMEM173/STING impairs the ability of TMEM173/STING to sense cytosolic DNA and promote the production of type I interferon (IFN-alpha and IFN-beta).[HAMAP-Rule:MF_04004]
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[[Category: Clements, A.]]
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== Evolutionary Conservation ==
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[[Category: Liu, X.]]
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[[Image:Consurf_key_small.gif|200px|right]]
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[[Category: Marmorstein, R.]]
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Check<jmol>
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[[Category: Zhao, K.]]
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<jmolCheckbox>
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[[Category: ZN]]
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/b9/2b9d_consurf.spt"</scriptWhenChecked>
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[[Category: homodimer]]
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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[[Category: zinc finger]]
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 08:39:15 2007''
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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=2b9d ConSurf].
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<div style="clear:both"></div>
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__TOC__
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</StructureSection>
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[[Category: Human papillomavirus type 1a]]
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[[Category: Large Structures]]
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[[Category: Clements A]]
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[[Category: Liu X]]
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[[Category: Marmorstein R]]
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[[Category: Zhao K]]

Current revision

Crystal Structure of HPV E7 CR3 domain

PDB ID 2b9d

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