2wh6: Difference between revisions
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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=''> | |||
== Structural highlights == | |||
<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='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='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'>[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> | |||
== Function == | |||
[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;"> | |||
== 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<ref>PMID:21203485</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2wh6" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | [[Category: Epstein-barr virus strain ag876]] | ||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
== | [[Category: Colman PM]] | ||
< | [[Category: Huang DCS]] | ||
[[Category: | [[Category: Kvansakul M]] | ||
[[Category: Colman | |||
[[Category: Huang | |||
[[Category: Kvansakul | |||
Latest revision as of 10:16, 9 August 2023
Crystal structure of anti-apoptotic BHRF1 in complex with the Bim BH3 domainCrystal structure of anti-apoptotic BHRF1 in complex with the Bim BH3 domain
Structural highlights
FunctionEAR_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 PubMedEpstein-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
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