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| - | ==CRYSTAL STRUCTURE OF ANTI-APOPTOTIC BHRF1 IN COMPLEX WITH THE BIM BH3 DOMAIN== | + | |
| - | <StructureSection load='2wh6' size='340' side='right' caption='[[2wh6]], [[Resolution|resolution]] 1.50Å' scene=''> | + | ==Crystal structure of anti-apoptotic BHRF1 in complex with the Bim BH3 domain== |
| | + | <StructureSection load='2wh6' size='340' side='right'caption='[[2wh6]], [[Resolution|resolution]] 1.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2wh6]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human_herpesvirus_4 Human herpesvirus 4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WH6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2WH6 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2wh6]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Epstein-barr_virus_strain_ag876 Epstein-barr virus strain ag876] 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=2WH6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WH6 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BR:BROMIDE+ION'>BR</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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]] 1.5Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2vm6|2vm6]], [[1q59|1q59]], [[2v6q|2v6q]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BR:BROMIDE+ION'>BR</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=2wh6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wh6 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2wh6 RCSB], [http://www.ebi.ac.uk/pdbsum/2wh6 PDBsum]</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=2wh6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wh6 OCA], [https://pdbe.org/2wh6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2wh6 RCSB], [https://www.ebi.ac.uk/pdbsum/2wh6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2wh6 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/EAR_EBV EAR_EBV]] Prevents premature death of the host cell during virus production, which would otherwise reduce the amount of progeny virus. Acts as a host B-cell leukemia/lymphoma 2 (Bcl-2) homolog, and interacts with pro-apoptotic proteins to prevent mitochondria permeabilization, release of cytochrome c and subsequent apoptosis of the host cell. [[http://www.uniprot.org/uniprot/B2L11_HUMAN B2L11_HUMAN]] Induces apoptosis and anoikis. Isoform BimL is more potent than isoform BimEL. Isoform Bim-alpha1, isoform Bim-alpha2 and isoform Bim-alpha3 induce apoptosis, although less potent than isoform BimEL, isoform BimL and isoform BimS. Isoform Bim-gamma induces apoptosis. Isoform Bim-alpha3 induces apoptosis possibly through a caspase-mediated pathway. Isoform BimAC and isoform BimABC lack the ability to induce apoptosis.<ref>PMID:9430630</ref> <ref>PMID:11734221</ref> <ref>PMID:12019181</ref> <ref>PMID:11997495</ref> <ref>PMID:15147734</ref> <ref>PMID:15486195</ref> | + | [https://www.uniprot.org/uniprot/EAR_EBVA8 EAR_EBVA8] Prevents premature death of the host cell during virus production, which would otherwise reduce the amount of progeny virus. Acts as a host B-cell leukemia/lymphoma 2 (Bcl-2) homolog, and interacts with pro-apoptotic proteins to prevent mitochondria permeabilization, release of cytochrome c and subsequent apoptosis of the host cell (By similarity). |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 2wh6" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human herpesvirus 4]] | + | [[Category: Epstein-barr virus strain ag876]] |
| - | [[Category: Colman, P M]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Huang, D C.S]] | + | [[Category: Large Structures]] |
| - | [[Category: Kvansakul, M]] | + | [[Category: Colman PM]] |
| - | [[Category: Apoptosis]] | + | [[Category: Huang DCS]] |
| - | [[Category: Early protein]] | + | [[Category: Kvansakul M]] |
| - | [[Category: Mitochondrion]]
| + | |
| - | [[Category: Transmembrane]]
| + | |
| - | [[Category: Viral protein]]
| + | |
| Structural highlights
Function
EAR_EBVA8 Prevents premature death of the host cell during virus production, which would otherwise reduce the amount of progeny virus. Acts as a host B-cell leukemia/lymphoma 2 (Bcl-2) homolog, and interacts with pro-apoptotic proteins to prevent mitochondria permeabilization, release of cytochrome c and subsequent apoptosis of the host cell (By similarity).
Publication Abstract from PubMed
Epstein-Barr virus (EBV) is associated with human malignancies, especially those affecting the B cell compartment such as Burkitt lymphoma. The virally encoded homolog of the mammalian pro-survival protein Bcl-2, BHRF1 contributes to viral infectivity and lymphomagenesis. In addition to the pro-apoptotic BH3-only protein Bim, its key target in lymphoid cells, BHRF1 also binds a selective sub-set of pro-apoptotic proteins (Bid, Puma, Bak) expressed by host cells. A consequence of BHRF1 expression is marked resistance to a range of cytotoxic agents and in particular, we show that its expression renders a mouse model of Burkitt lymphoma untreatable. As current small organic antagonists of Bcl-2 do not target BHRF1, the structures of it in complex with Bim or Bak shown here will be useful to guide efforts to target BHRF1 in EBV-associated malignancies, which are usually associated with poor clinical outcomes.
Structural Basis for Apoptosis Inhibition by Epstein-Barr Virus BHRF1.,Kvansakul M, Wei AH, Fletcher JI, Willis SN, Chen L, Roberts AW, Huang DC, Colman PM PLoS Pathog. 2010 Dec 23;6(12):e1001236. PMID:21203485[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kvansakul M, Wei AH, Fletcher JI, Willis SN, Chen L, Roberts AW, Huang DC, Colman PM. Structural Basis for Apoptosis Inhibition by Epstein-Barr Virus BHRF1. PLoS Pathog. 2010 Dec 23;6(12):e1001236. PMID:21203485 doi:10.1371/journal.ppat.1001236
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