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| | ==THE 3.1 ANGSTROM RESOLUTION CRYSTAL STRUCTURE OF A MUTATED BACULOVIRUS P35 AFTER CASPASE CLEAVAGE== | | ==THE 3.1 ANGSTROM RESOLUTION CRYSTAL STRUCTURE OF A MUTATED BACULOVIRUS P35 AFTER CASPASE CLEAVAGE== |
| - | <StructureSection load='1i3p' size='340' side='right' caption='[[1i3p]], [[Resolution|resolution]] 3.10Å' scene=''> | + | <StructureSection load='1i3p' size='340' side='right'caption='[[1i3p]], [[Resolution|resolution]] 3.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1i3p]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Acmnpv Acmnpv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1I3P OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1I3P FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1i3p]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Autographa_californica_nucleopolyhedrovirus Autographa californica nucleopolyhedrovirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1I3P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1I3P FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1p35|1p35]]</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]] 3.1Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">P35 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=46015 AcMNPV])</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=1i3p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1i3p OCA], [https://pdbe.org/1i3p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1i3p RCSB], [https://www.ebi.ac.uk/pdbsum/1i3p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1i3p 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=1i3p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1i3p OCA], [http://pdbe.org/1i3p PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1i3p RCSB], [http://www.ebi.ac.uk/pdbsum/1i3p PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1i3p ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/VP35_NPVAC VP35_NPVAC]] Blocks the insect or worm host cells apoptotic response initiated by the viral infection. Confers protection from cell death in mammalian cells. Acts by blocking the activity of members of the caspase family of proteases. Required for late and very late gene expression. | + | [https://www.uniprot.org/uniprot/P35_NPVAC P35_NPVAC] Functions as an inhibitor of the host RNA interference antiviral response. Inhibits the insect host cell apoptotic response initiated by the viral infection. Blocks as well the activity of members of the caspase family of proteases. Required for late and very late gene expression.<ref>PMID:16081248</ref> <ref>PMID:1962198</ref> <ref>PMID:26018163</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Acmnpv]] | + | [[Category: Autographa californica nucleopolyhedrovirus]] |
| - | [[Category: Cruz, W P.dela]] | + | [[Category: Large Structures]] |
| - | [[Category: Fisher, A J]] | + | [[Category: Fisher AJ]] |
| - | [[Category: Friesen, P D]] | + | [[Category: Friesen PD]] |
| - | [[Category: Lemongello, D]] | + | [[Category: Lemongello D]] |
| - | [[Category: Apoptosis]] | + | [[Category: Dela Cruz WP]] |
| - | [[Category: Hairpin loop]]
| + | |
| - | [[Category: Helix-turn-helix]]
| + | |
| - | [[Category: Reactive site loop]]
| + | |
| Structural highlights
Function
P35_NPVAC Functions as an inhibitor of the host RNA interference antiviral response. Inhibits the insect host cell apoptotic response initiated by the viral infection. Blocks as well the activity of members of the caspase family of proteases. Required for late and very late gene expression.[1] [2] [3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Baculovirus P35 is a universal suppressor of apoptosis that stoichiometrically inhibits cellular caspases in a novel cleavage-dependent mechanism. Upon caspase cleavage at Asp-87, the 10- and 25-kDa cleavage products of P35 remain tightly associated with the inhibited caspase. Mutations in the alpha-helix of the reactive site loop preceding the cleavage site abrogate caspase inhibition and antiapoptotic activity. Substitution of Pro for Val-71, which is located in the middle of this alpha-helix, produces a protein that is cleaved at the requisite Asp-87 but does not remain bound to the caspase. This loss-of-function mutation provided the opportunity to structurally analyze the conformational changes of the P35 reactive site loop after caspase cleavage. We report here the 2.7 A resolution crystal structure of V71P-mutated P35 after cleavage by human caspase-3. The structure reveals a large movement in the carboxyl-terminal side of the reactive site loop that swings down and forms a new beta-strand that augments an existing beta-sheet. Additionally, the hydrophobic amino terminus releases and extends away from the protein core. Similar movements occur when P35 forms an inhibitory complex with human caspase-8. These findings suggest that the alpha-helix mutation may alter the sequential steps or kinetics of the conformational changes required for inhibition, thereby causing P35 loss of function.
Crystal structure of baculovirus P35 reveals a novel conformational change in the reactive site loop after caspase cleavage.,dela Cruz WP, Friesen PD, Fisher AJ J Biol Chem. 2001 Aug 31;276(35):32933-9. Epub 2001 Jun 11. PMID:11402050[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ da Silveira EB, Cordeiro BA, Ribeiro BM, Báo SN. In vivo apoptosis induction and reduction of infectivity by an Autographa californica multiple nucleopolyhedrovirus p35(-) recombinant in hemocytes from the velvet bean caterpillar Anticarsia gemmatalis (Hübner) (Lepidoptera: Noctuidae). Res Microbiol. 2005 Dec;156(10):1014-25. PMID:16081248 doi:10.1016/j.resmic.2005.06.001
- ↑ Clem RJ, Fechheimer M, Miller LK. Prevention of apoptosis by a baculovirus gene during infection of insect cells. Science. 1991 Nov 29;254(5036):1388-90. PMID:1962198 doi:10.1126/science.1962198
- ↑ Mehrabadi M, Hussain M, Matindoost L, Asgari S. The Baculovirus Antiapoptotic p35 Protein Functions as an Inhibitor of the Host RNA Interference Antiviral Response. J Virol. 2015 Aug;89(16):8182-92. PMID:26018163 doi:10.1128/JVI.00802-15
- ↑ dela Cruz WP, Friesen PD, Fisher AJ. Crystal structure of baculovirus P35 reveals a novel conformational change in the reactive site loop after caspase cleavage. J Biol Chem. 2001 Aug 31;276(35):32933-9. Epub 2001 Jun 11. PMID:11402050 doi:10.1074/jbc.M103930200
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