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| | <StructureSection load='6trr' size='340' side='right'caption='[[6trr]], [[Resolution|resolution]] 2.12Å' scene=''> | | <StructureSection load='6trr' size='340' side='right'caption='[[6trr]], [[Resolution|resolution]] 2.12Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6trr]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Tanapox_virus_strain_davis Tanapox virus strain davis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TRR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6TRR FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6trr]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Yaba-like_disease_virus Yaba-like disease virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TRR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6TRR FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</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]] 2.1200736Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">16L ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=132475 Tanapox virus strain Davis])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene></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=6trr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6trr OCA], [https://pdbe.org/6trr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6trr RCSB], [https://www.ebi.ac.uk/pdbsum/6trr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6trr 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=6trr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6trr OCA], [https://pdbe.org/6trr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6trr RCSB], [https://www.ebi.ac.uk/pdbsum/6trr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6trr ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://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/Q9DHU6_YLDV Q9DHU6_YLDV] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Tanapox virus strain davis]] | + | [[Category: Yaba-like disease virus]] |
| - | [[Category: Hinds, M G]] | + | [[Category: Hinds MG]] |
| - | [[Category: Kvansakul, M]] | + | [[Category: Kvansakul M]] |
| - | [[Category: Suraweera, C D]] | + | [[Category: Suraweera CD]] |
| - | [[Category: Apoptosis]]
| + | |
| - | [[Category: Bcl-2]]
| + | |
| - | [[Category: Pox virus]]
| + | |
| Structural highlights
Function
Q9DHU6_YLDV
Publication Abstract from PubMed
Premature programmed cell death or apoptosis of cells is a strategy utilized by multicellular organisms to counter microbial threats. Tanapoxvirus (TANV) is a large double-stranded DNA virus belonging to the poxviridae that causes mild monkeypox-like infections in humans and primates. TANV encodes for a putative apoptosis inhibitory protein 16L. We show that TANV16L is able to bind to a range of peptides spanning the BH3 motif of human proapoptotic Bcl-2 proteins and is able to counter growth arrest of yeast induced by human Bak and Bax. We then determined the crystal structures of TANV16L bound to three identified interactors, Bax, Bim and Puma BH3. TANV16L adopts a globular Bcl-2 fold comprising 7 alpha-helices and utilizes the canonical Bcl-2 binding groove to engage proapoptotic host cell Bcl-2 proteins. Unexpectedly, TANV16L is able to adopt both a monomeric and a domain-swapped dimeric topology where the alpha1 helix from one protomer is swapped into a neighbouring unit. Despite adopting two different oligomeric forms, the canonical ligand binding groove in TANV16L remains unchanged from monomer to domain-swapped dimer. Our results provide a structural and mechanistic basis for tanapoxvirus-mediated inhibition of host cell apoptosis and reveal the capacity of Bcl-2 proteins to adopt differential oligomeric states whilst maintaining the canonical ligand binding groove in an unchanged state. DATABASE: Structural data are available in the Protein Data Bank (PDB) under the accession numbers 6TPQ, 6TQQ and 6TRR.
Structural insight into tanapoxvirus-mediated inhibition of apoptosis.,Suraweera CD, Anasir MI, Chugh S, Javorsky A, Impey RE, Hasan Zadeh M, Soares da Costa TP, Hinds MG, Kvansakul M FEBS J. 2020 Sep;287(17):3733-3750. doi: 10.1111/febs.15365. Epub 2020 May 31. PMID:32412687[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Suraweera CD, Anasir MI, Chugh S, Javorsky A, Impey RE, Hasan Zadeh M, Soares da Costa TP, Hinds MG, Kvansakul M. Structural insight into tanapoxvirus-mediated inhibition of apoptosis. FEBS J. 2020 Sep;287(17):3733-3750. doi: 10.1111/febs.15365. Epub 2020 May 31. PMID:32412687 doi:http://dx.doi.org/10.1111/febs.15365
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