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5ua5

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Crystal structure of A179L:Bid BH3 complex

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 <StructureSection load='5ua5' size='340' side='right'caption='[[5ua5]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5ua5]] 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=5UA5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UA5 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5ua5]] 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=5UA5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5UA5 FirstGlance]. <br>
-</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5ua4|5ua4]]</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]] 2.5&#8491;</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=5ua5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ua5 OCA], [https://pdbe.org/5ua5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ua5 RCSB], [https://www.ebi.ac.uk/pdbsum/5ua5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ua5 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=5ua5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ua5 OCA], [http://pdbe.org/5ua5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ua5 RCSB], [http://www.ebi.ac.uk/pdbsum/5ua5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ua5 ProSAT]</span></td></tr>
 </table>
-<div style="background-color:#fffaf0;">
+== Function ==
-== Publication Abstract from PubMed ==
+[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>
-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.
-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>
-From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-</div>
-<div class="pdbe-citations 5ua5" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Asf]]
+[[Category: African swine fever virus]]
 [[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]]

5ua5

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Crystal structure of A179L:Bid BH3 complex

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