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| | ==NMR structure of the C-terminal domain (dimer) of HPV45 oncoprotein E7== | | ==NMR structure of the C-terminal domain (dimer) of HPV45 oncoprotein E7== |
| - | <StructureSection load='2f8b' size='340' side='right'caption='[[2f8b]], [[NMR_Ensembles_of_Models | 15 NMR models]]' scene=''> | + | <StructureSection load='2f8b' size='340' side='right'caption='[[2f8b]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2f8b]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Hpv45 Hpv45]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2F8B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2F8B FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2f8b]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_papillomavirus_45 Human papillomavirus 45]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2F8B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2F8B FirstGlance]. <br> |
| - | </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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2ewl|2ewl]]</div></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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">E7 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10593 HPV45])</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=2f8b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2f8b OCA], [https://pdbe.org/2f8b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2f8b RCSB], [https://www.ebi.ac.uk/pdbsum/2f8b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2f8b ProSAT]</span></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=2f8b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2f8b OCA], [https://pdbe.org/2f8b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2f8b RCSB], [https://www.ebi.ac.uk/pdbsum/2f8b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2f8b ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/VE7_HPV45 VE7_HPV45]] 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_HPV45 VE7_HPV45] 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). |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Hpv45]] | + | [[Category: Human papillomavirus 45]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Gorlach, M]] | + | [[Category: Gorlach M]] |
| - | [[Category: Ohlenschlager, O]] | + | [[Category: Ohlenschlager O]] |
| - | [[Category: Dimer]]
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| - | [[Category: E7]]
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| - | [[Category: Hpv]]
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| - | [[Category: Oncoprotein]]
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| - | [[Category: Virus-viral protein complex]]
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| - | [[Category: Zinc binding]]
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| Structural highlights
Function
VE7_HPV45 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).
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The oncoprotein E7 of human papilloma viruses (HPV) is involved in the pathogenesis and maintenance of human cervical cancers. The most prevalent HPV types found in cervix carcinomas are HPV16, 18 and 45. The structure of the E7 dimer from HPV45 (PDB 2F8B) was determined by nuclear magnetic resonance spectroscopy. Each monomer comprises an unfolded N-terminus and a well-structured C-terminal domain with a beta1beta2alpha1beta3alpha2 topology representing a unique zinc-binding fold found only for E7. Dimerization occurs through the alpha1/alpha1' helices and intermolecular beta-sheet formation but excludes the zinc-binding sites. E7 is reported to interact with a number of cellular proteins (e.g. pRb, p21(CIP1)). Binding of a peptide derived from the C-terminus of p21(CIP1) to the C-terminal domain of E7 was characterized by monitoring chemical shift perturbations of the amide groups of E7. This provides direct evidence that a shallow groove situated between alpha1 and beta1 of the E7 C-terminal domain is interacting with the C-terminus of p21(CIP1). Intriguingly, this binding site overlaps with the low-affinity binding site on E7 for the C-domain of pRb.
Solution structure of the partially folded high-risk human papilloma virus 45 oncoprotein E7.,Ohlenschlager O, Seiboth T, Zengerling H, Briese L, Marchanka A, Ramachandran R, Baum M, Korbas M, Meyer-Klaucke W, Durst M, Gorlach M Oncogene. 2006 Sep 28;25(44):5953-9. Epub 2006 Apr 24. PMID:16636661[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Ohlenschlager O, Seiboth T, Zengerling H, Briese L, Marchanka A, Ramachandran R, Baum M, Korbas M, Meyer-Klaucke W, Durst M, Gorlach M. Solution structure of the partially folded high-risk human papilloma virus 45 oncoprotein E7. Oncogene. 2006 Sep 28;25(44):5953-9. Epub 2006 Apr 24. PMID:16636661
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