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6tqp

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Revision as of 15:18, 8 June 2021

Structural insight into tanapoxvirus mediated inhibition of apoptosis

Structural highlights

6tqp is a 2 chain structure with sequence from Tanapox virus strain davis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	16L (Tanapox virus strain Davis)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[BBC3_HUMAN] Essential mediator of p53/TP53-dependent and p53/TP53-independent apoptosis. Functions by promoting partial unfolding of BCL2L1 and dissociation of BCL2L1 from p53/TP53. Regulates ER stress-induced neuronal apoptosis.^[1] ^[2]

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^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Yu J, Zhang L, Hwang PM, Kinzler KW, Vogelstein B. PUMA induces the rapid apoptosis of colorectal cancer cells. Mol Cell. 2001 Mar;7(3):673-82. PMID:11463391
↑ Follis AV, Chipuk JE, Fisher JC, Yun MK, Grace CR, Nourse A, Baran K, Ou L, Min L, White SW, Green DR, Kriwacki RW. PUMA binding induces partial unfolding within BCL-xL to disrupt p53 binding and promote apoptosis. Nat Chem Biol. 2013 Jan 20. doi: 10.1038/nchembio.1166. PMID:23340338 doi:http://dx.doi.org/10.1038/nchembio.1166
↑ 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

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6tqp"

@@ Line 3: / Line 3: @@
 <StructureSection load='6tqp' size='340' side='right'caption='[[6tqp]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6tqp]] is a 2 chain structure with sequence from [http://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=6TQP OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6TQP FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6tqp]] 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=6TQP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6TQP 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>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">16L ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=132475 Tanapox virus strain Davis])</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6tqp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6tqp OCA], [http://pdbe.org/6tqp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6tqp RCSB], [http://www.ebi.ac.uk/pdbsum/6tqp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6tqp 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=6tqp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6tqp OCA], [https://pdbe.org/6tqp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6tqp RCSB], [https://www.ebi.ac.uk/pdbsum/6tqp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6tqp ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/BBC3_HUMAN BBC3_HUMAN]] Essential mediator of p53/TP53-dependent and p53/TP53-independent apoptosis. Functions by promoting partial unfolding of BCL2L1 and dissociation of BCL2L1 from p53/TP53. Regulates ER stress-induced neuronal apoptosis.<ref>PMID:11463391</ref> <ref>PMID:23340338</ref>
+[[https://www.uniprot.org/uniprot/BBC3_HUMAN BBC3_HUMAN]] Essential mediator of p53/TP53-dependent and p53/TP53-independent apoptosis. Functions by promoting partial unfolding of BCL2L1 and dissociation of BCL2L1 from p53/TP53. Regulates ER stress-induced neuronal apoptosis.<ref>PMID:11463391</ref> <ref>PMID:23340338</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==

6tqp

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Revision as of 15:18, 8 June 2021

Structural insight into tanapoxvirus mediated inhibition of apoptosis

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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