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| | <StructureSection load='5tzp' size='340' side='right'caption='[[5tzp]], [[Resolution|resolution]] 1.35Å' scene=''> | | <StructureSection load='5tzp' size='340' side='right'caption='[[5tzp]], [[Resolution|resolution]] 1.35Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5tzp]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Fowpn Fowpn]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TZP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TZP FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5tzp]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Fowlpox_virus_strain_NVSL Fowlpox virus strain NVSL] and [https://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TZP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5TZP FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 1.35Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5tzq|5tzq]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">FPV039 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=928301 FOWPN])</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=5tzp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tzp OCA], [https://pdbe.org/5tzp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5tzp RCSB], [https://www.ebi.ac.uk/pdbsum/5tzp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5tzp 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=5tzp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tzp OCA], [http://pdbe.org/5tzp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5tzp RCSB], [http://www.ebi.ac.uk/pdbsum/5tzp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5tzp ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| - | <div style="background-color:#fffaf0;">
| + | == Function == |
| - | == Publication Abstract from PubMed == | + | [https://www.uniprot.org/uniprot/ARBH_FOWPN ARBH_FOWPN] Plays a role in the inhibition of host apoptosis by sequestering and inactivating multiple proapoptotic BCL-2 proteins, including BAK1 and BAX.<ref>PMID:19439472</ref> |
| - | Programmed cell death or apoptosis of infected host cells is an important defense mechanism in response to viral infections. This process is regulated by pro-apoptotic and pro-survival members of the B-cell lymphoma 2 (Bcl-2) protein family. To counter premature death of a virus-infected cell, poxviruses use a range of different molecular strategies, including the mimicry of pro-survival Bcl-2 proteins. One such viral pro-survival protein is the fowlpox virus protein FPV039, which is a potent apoptosis inhibitor, but the precise molecular mechanism by which FPV039 inhibits apoptosis is unknown. To understand how fowlpox virus inhibits apoptosis we examined FPV039 using isothermal titration calorimetry, small-angle X-ray scattering and X-ray crystallography. Here, we report that the fowlpox virus pro-survival protein FPV039 promiscuously binds to cellular pro-apoptotic Bcl-2, and engages all major pro-apoptotic Bcl-2 proteins. Unlike other identified viral Bcl-2 proteins to date, FPV039 engaged with cellular pro-apoptotic Bcl-2 with affinities comparable to those of Bcl-2's endogenous cellular counterparts. Structural studies revealed that FPV039 adopts the conserved Bcl-2 fold observed in cellular pro-survival Bcl-2 proteins, and closely mimics the structure of the pro-survival Bcl-2 family protein Mcl-1. Our findings suggest that FPV039 is a pan Bcl-2 protein inhibitor that can engage all host BH3-only proteins as well as Bcl-2 associated X, apoptosis regulator (Bax) and Bcl-2 antagonist/killer (Bak) proteins to inhibit premature apoptosis of an infected host cell. This work therefore provides a mechanistic platform to better understand FPV039-mediated apoptosis inhibition.
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| - | Structural Basis of Apoptosis Inhibition by the Fowlpox Virus Protein FPV039.,Anasir MI, Caria S, Skinner MA, Kvansakul M J Biol Chem. 2017 Apr 14. pii: jbc.M116.768879. doi: 10.1074/jbc.M116.768879. PMID:28411240<ref>PMID:28411240</ref>
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| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 5tzp" style="background-color:#fffaf0;"></div>
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| | | | |
| | ==See Also== | | ==See Also== |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Fowpn]] | + | [[Category: Fowlpox virus strain NVSL]] |
| | + | [[Category: Gallus gallus]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Anasir, M I]] | + | [[Category: Anasir MI]] |
| - | [[Category: Kvansakul, M]] | + | [[Category: Kvansakul M]] |
| - | [[Category: Apoptosis]]
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| - | [[Category: Bcl-2]]
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| - | [[Category: Bh3-only]]
| + | |
| - | [[Category: Fowlpox]]
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| - | [[Category: Poxvirus]]
| + | |
