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| | <StructureSection load='5ua4' size='340' side='right'caption='[[5ua4]], [[Resolution|resolution]] 2.60Å' scene=''> | | <StructureSection load='5ua4' size='340' side='right'caption='[[5ua4]], [[Resolution|resolution]] 2.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5ua4]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Asf Asf]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UA4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UA4 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5ua4]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/African_swine_fever_virus African swine fever virus] and [https://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UA4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5UA4 FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5ua5|5ua5]]</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]] 2.6Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">5-HL, A179L ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10497 ASF])</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=5ua4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ua4 OCA], [https://pdbe.org/5ua4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ua4 RCSB], [https://www.ebi.ac.uk/pdbsum/5ua4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ua4 ProSAT]</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=5ua4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ua4 OCA], [http://pdbe.org/5ua4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ua4 RCSB], [http://www.ebi.ac.uk/pdbsum/5ua4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ua4 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/BID_PIG BID_PIG]] Induces caspases and apoptosis. Counters the protective effect of Bcl-2 (By similarity). | + | [https://www.uniprot.org/uniprot/ARBH_ASFB7 ARBH_ASFB7] Suppresses apoptosis in host cell and thus facilitates production of progeny virions (PubMed:9123849, PubMed:18329683). Has the ability to potentially bind to all the members of the proapoptotic Bcl-2 family (PubMed:28053104, PubMed:18329683).<ref>PMID:18329683</ref> <ref>PMID:28053104</ref> <ref>PMID:9123849</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | Programmed cell death is a tightly controlled process critical for the removal of damaged or infected cells. Pro- and anti-apoptotic proteins of the Bcl-2 family are pivotal mediators of this process. African Swine Fever virus (ASFV) is a large DNA virus, the only member of the Asfarviridae family, and harbors A179L, a putative Bcl-2 like protein. A179L has been shown to bind to several pro-apoptotic Bcl-2 proteins, however the hierarchy of binding and the structural basis for apoptosis inhibition are currently not understood. We systematically evaluated the ability of A179L to bind pro-apoptotic Bcl-2 family members, and show that A179L is the first anti-apoptotic Bcl-2 protein to bind to all major death inducing mammalian Bcl-2 proteins. We then defined the structural basis for apoptosis inhibition of A179L by determining crystal structures of A179L bound to both Bid and Bax BH3 motifs. Our findings provide a mechanistic understanding for the potent anti-apoptotic activity of A179L by identifying it as the first pan pro-death Bcl-2 binder, and serve as a platform for more detailed investigations into the role of A179L during ASFV infection. IMPORTANCE: Numerous viruses have acquired strategies to subvert apoptosis by encoding proteins capable of sequestering pro-apoptotic host proteins. African Swine Fever virus (ASFV), a large DNA virus and the only member of the Asfarviridae family, encodes the protein A179L that functions to prevent apoptosis. We show that A179L is unusual amongst anti-apoptotic Bcl-2 proteins in being able to physically bind to all core death inducing mammalian Bcl-2 proteins. Currently, little is known regarding the molecular interactions between A179L and the pro-apoptotic Bcl-2 members. Using crystal structures of A179L bound to two of the identified pro-apoptotic Bcl-2 proteins, Bid and Bax, we now provide a 3D view of how A179L sequesters host pro-apoptotic proteins, which is crucial for subverting premature host cell apoptosis.
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| - | Structural insight into African Swine Fever virus A179L mediated inhibition of apoptosis.,Banjara S, Caria S, Dixon LK, Hinds MG, Kvansakul M J Virol. 2017 Jan 4. pii: JVI.02228-16. doi: 10.1128/JVI.02228-16. PMID:28053104<ref>PMID:28053104</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div> | + | |
| - | <div class="pdbe-citations 5ua4" style="background-color:#fffaf0;"></div> | + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Asf]] | + | [[Category: African swine fever virus]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Banjara, S]] | + | [[Category: Sus scrofa]] |
| - | [[Category: Caria, S]] | + | [[Category: Banjara S]] |
| - | [[Category: Kvansakul, M]] | + | [[Category: Caria S]] |
| - | [[Category: Apoptosis]] | + | [[Category: Kvansakul M]] |
| - | [[Category: Bcl-2]]
| + | |
