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2b9d

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Revision as of 16:07, 12 October 2017

Crystal Structure of HPV E7 CR3 domain

Structural highlights

2b9d is a 2 chain structure with sequence from Hpv1a. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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).

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 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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Liu X, Clements A, Zhao K, Marmorstein R. Structure of the human Papillomavirus E7 oncoprotein and its mechanism for inactivation of the retinoblastoma tumor suppressor. J Biol Chem. 2006 Jan 6;281(1):578-86. Epub 2005 Oct 24. PMID:16249186 doi:10.1074/jbc.M508455200

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2b9d"

@@ Line 1: / Line 1: @@
 ==Crystal Structure of HPV E7 CR3 domain==
 <StructureSection load='2b9d' size='340' side='right' caption='[[2b9d]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
@@ Line 4: / Line 5: @@
 <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>
 </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>
-<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='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], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2b9d ProSAT]</span></td></tr>
 </table>
 == Function ==

2b9d

From Proteopedia

Revision as of 16:07, 12 October 2017

Crystal Structure of HPV E7 CR3 domain

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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