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==Crystal Structure of HPV E7 CR3 domain==
==Crystal Structure of HPV E7 CR3 domain==
<StructureSection load='2b9d' size='340' side='right' caption='[[2b9d]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
<StructureSection load='2b9d' size='340' side='right'caption='[[2b9d]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[2b9d]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Hpv1a Hpv1a]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2B9D FirstGlance]. <br>
<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>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
</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>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2b9d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2b9d OCA], [http://pdbe.org/2b9d PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2b9d RCSB], [http://www.ebi.ac.uk/pdbsum/2b9d PDBsum]</span></td></tr>
<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>
<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>
</table>
</table>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/VE7_HPV1A VE7_HPV1A]] E7 protein has both transforming and trans-activating activities. Disrupts the function of host retinoblastoma protein RB1/pRb, which is a key regulator of the cell cycle. Induces the disassembly of the E2F1 transcription factors from RB1, with subsequent transcriptional activation of E2F1-regulated S-phase genes. Inactivation of the ability of RB1 to arrest the cell cycle is critical for cellular transformation, uncontrolled cellular growth and proliferation induced by viral infection. Stimulation of progression from G1 to S phase allows the virus to efficiently use the cellular DNA replicating machinery to achieve viral genome replication. Interferes with histone deacetylation mediated by HDAC1 and HDAC2, leading to activation of transcription (By similarity).  
[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]
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
Check<jmol>
   <jmolCheckbox>
   <jmolCheckbox>
     <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/b9/2b9d_consurf.spt"</scriptWhenChecked>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/b9/2b9d_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
     <text>to colour the structure by Evolutionary Conservation</text>
Line 18: Line 20:
</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].
</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].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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.
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:16249186<ref>PMID:16249186</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2b9d" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Hpv1a]]
[[Category: Human papillomavirus type 1a]]
[[Category: Clements, A]]
[[Category: Large Structures]]
[[Category: Liu, X]]
[[Category: Clements A]]
[[Category: Marmorstein, R]]
[[Category: Liu X]]
[[Category: Zhao, K]]
[[Category: Marmorstein R]]
[[Category: Homodimer]]
[[Category: Zhao K]]
[[Category: Transcription]]
[[Category: Viral protein]]
[[Category: Zinc finger]]

Latest revision as of 12:16, 14 February 2024

Crystal Structure of HPV E7 CR3 domainCrystal Structure of HPV E7 CR3 domain

Structural highlights

2b9d is a 2 chain structure with sequence from Human papillomavirus type 1a. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.6Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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]

Evolutionary Conservation

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

2b9d, resolution 1.60Å

Drag the structure with the mouse to rotate

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OCA
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