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| | <StructureSection load='4uf2' size='340' side='right'caption='[[4uf2]], [[Resolution|resolution]] 3.00Å' scene=''> | | <StructureSection load='4uf2' size='340' side='right'caption='[[4uf2]], [[Resolution|resolution]] 3.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4uf2]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Deerpox_virus Deerpox virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4UF2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4UF2 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4uf2]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Deerpox_virus_W-1170-84 Deerpox virus W-1170-84] 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=4UF2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4UF2 FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4uf1|4uf1]], [[4uf3|4uf3]]</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]] 3Å</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=4uf2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4uf2 OCA], [http://pdbe.org/4uf2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4uf2 RCSB], [http://www.ebi.ac.uk/pdbsum/4uf2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4uf2 ProSAT]</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=4uf2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4uf2 OCA], [https://pdbe.org/4uf2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4uf2 RCSB], [https://www.ebi.ac.uk/pdbsum/4uf2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4uf2 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/BAX_HUMAN BAX_HUMAN]] Accelerates programmed cell death by binding to, and antagonizing the apoptosis repressor BCL2 or its adenovirus homolog E1B 19k protein. Under stress conditions, undergoes a conformation change that causes translocation to the mitochondrion membrane, leading to the release of cytochrome c that then triggers apoptosis. Promotes activation of CASP3, and thereby apoptosis.<ref>PMID:8358790</ref> <ref>PMID:10772918</ref> <ref>PMID:8521816</ref> <ref>PMID:16113678</ref> <ref>PMID:18948948</ref> <ref>PMID:21199865</ref> | + | [https://www.uniprot.org/uniprot/DPV22_DPV83 DPV22_DPV83] Plays a role in the inhibition of host apoptosis by sequestering and inactivating several proapoptotic BCL-2 proteins, including BAK1 and BAX. Prevents the conformational activation of both of them.<ref>PMID:21159883</ref> |
| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed ==
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| - | Apoptosis is a key innate defence mechanism to eliminate virally infected cells. To counteract premature host-cell apoptosis, poxviruses have evolved numerous molecular strategies, including the use of Bcl-2 proteins, to ensure their own survival. Here, it is reported that the Deerpox virus inhibitor of apoptosis, DPV022, only engages a highly restricted set of death-inducing Bcl-2 proteins, including Bim, Bax and Bak, with modest affinities. Structural analysis reveals that DPV022 adopts a Bcl-2 fold with a dimeric domain-swapped topology and binds pro-death Bcl-2 proteins via two conserved ligand-binding grooves found on opposite sides of the dimer. Structures of DPV022 bound to Bim, Bak and Bax BH3 domains reveal that a partial obstruction of the binding groove is likely to be responsible for the modest affinities of DPV022 for BH3 domains. These findings reveal that domain-swapped dimeric Bcl-2 folds are not unusual and may be found more widely in viruses. Furthermore, the modest affinities of DPV022 for pro-death Bcl-2 proteins suggest that two distinct classes of anti-apoptotic viral Bcl-2 proteins exist: those that are monomeric and tightly bind a range of death-inducing Bcl-2 proteins, and others such as DPV022 that are dimeric and only bind a very limited number of death-inducing Bcl-2 proteins with modest affinities.
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| - | Structural basis of Deerpox virus-mediated inhibition of apoptosis.,Burton DR, Caria S, Marshall B, Barry M, Kvansakul M Acta Crystallogr D Biol Crystallogr. 2015 Aug 1;71(Pt 8):1593-603. doi:, 10.1107/S1399004715009402. Epub 2015 Jul 28. PMID:26249341<ref>PMID:26249341</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| - | <div class="pdbe-citations 4uf2" style="background-color:#fffaf0;"></div>
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| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Deerpox virus]] | + | [[Category: Deerpox virus W-1170-84]] |
| | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Burton, D R]] | + | [[Category: Burton DR]] |
| - | [[Category: Kvansakul, M]] | + | [[Category: Kvansakul M]] |
| - | [[Category: Apoptosis]]
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| - | [[Category: Bax bh3]]
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| - | [[Category: Bcl-2]]
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| - | [[Category: Viral protein]]
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