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6tqq

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Revision as of 15:19, 8 June 2021

Structural insight into tanapoxvirus mediated inhibition of apoptosis

Structural highlights

6tqq 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:
Related:	6tqp
Gene:	16L (Tanapox virus strain Davis)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[B2L11_HUMAN] Induces apoptosis and anoikis. Isoform BimL is more potent than isoform BimEL. Isoform Bim-alpha1, isoform Bim-alpha2 and isoform Bim-alpha3 induce apoptosis, although less potent than isoform BimEL, isoform BimL and isoform BimS. Isoform Bim-gamma induces apoptosis. Isoform Bim-alpha3 induces apoptosis possibly through a caspase-mediated pathway. Isoform BimAC and isoform BimABC lack the ability to induce apoptosis.^[1] ^[2] ^[3] ^[4] ^[5] ^[6]

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^[7]

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

References

↑ O'Connor L, Strasser A, O'Reilly LA, Hausmann G, Adams JM, Cory S, Huang DC. Bim: a novel member of the Bcl-2 family that promotes apoptosis. EMBO J. 1998 Jan 15;17(2):384-95. PMID:9430630 doi:http://dx.doi.org/10.1093/emboj/17.2.384
↑ U M, Miyashita T, Shikama Y, Tadokoro K, Yamada M. Molecular cloning and characterization of six novel isoforms of human Bim, a member of the proapoptotic Bcl-2 family. FEBS Lett. 2001 Nov 30;509(1):135-41. PMID:11734221
↑ Liu JW, Chandra D, Tang SH, Chopra D, Tang DG. Identification and characterization of Bimgamma, a novel proapoptotic BH3-only splice variant of Bim. Cancer Res. 2002 May 15;62(10):2976-81. PMID:12019181
↑ Marani M, Tenev T, Hancock D, Downward J, Lemoine NR. Identification of novel isoforms of the BH3 domain protein Bim which directly activate Bax to trigger apoptosis. Mol Cell Biol. 2002 Jun;22(11):3577-89. PMID:11997495
↑ Chen JZ, Ji CN, Gu SH, Li JX, Zhao EP, Huang Y, Huang L, Ying K, Xie Y, Mao YM. Over-expression of Bim alpha3, a novel isoform of human Bim, result in cell apoptosis. Int J Biochem Cell Biol. 2004 Aug;36(8):1554-61. PMID:15147734 doi:http://dx.doi.org/10.1016/j.biocel.2003.12.015
↑ Fukazawa H, Noguchi K, Masumi A, Murakami Y, Uehara Y. BimEL is an important determinant for induction of anoikis sensitivity by mitogen-activated protein/extracellular signal-regulated kinase kinase inhibitors. Mol Cancer Ther. 2004 Oct;3(10):1281-8. PMID:15486195
↑ 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/6tqq"

@@ Line 3: / Line 3: @@
 <StructureSection load='6tqq' size='340' side='right'caption='[[6tqq]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6tqq]] 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=6TQQ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6TQQ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6tqq]] 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=6TQQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6TQQ 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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[6tqp|6tqp]]</div></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=6tqq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6tqq OCA], [http://pdbe.org/6tqq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6tqq RCSB], [http://www.ebi.ac.uk/pdbsum/6tqq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6tqq 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=6tqq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6tqq OCA], [https://pdbe.org/6tqq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6tqq RCSB], [https://www.ebi.ac.uk/pdbsum/6tqq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6tqq ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/B2L11_HUMAN B2L11_HUMAN]] Induces apoptosis and anoikis. Isoform BimL is more potent than isoform BimEL. Isoform Bim-alpha1, isoform Bim-alpha2 and isoform Bim-alpha3 induce apoptosis, although less potent than isoform BimEL, isoform BimL and isoform BimS. Isoform Bim-gamma induces apoptosis. Isoform Bim-alpha3 induces apoptosis possibly through a caspase-mediated pathway. Isoform BimAC and isoform BimABC lack the ability to induce apoptosis.<ref>PMID:9430630</ref> <ref>PMID:11734221</ref> <ref>PMID:12019181</ref> <ref>PMID:11997495</ref> <ref>PMID:15147734</ref> <ref>PMID:15486195</ref>
+[[https://www.uniprot.org/uniprot/B2L11_HUMAN B2L11_HUMAN]] Induces apoptosis and anoikis. Isoform BimL is more potent than isoform BimEL. Isoform Bim-alpha1, isoform Bim-alpha2 and isoform Bim-alpha3 induce apoptosis, although less potent than isoform BimEL, isoform BimL and isoform BimS. Isoform Bim-gamma induces apoptosis. Isoform Bim-alpha3 induces apoptosis possibly through a caspase-mediated pathway. Isoform BimAC and isoform BimABC lack the ability to induce apoptosis.<ref>PMID:9430630</ref> <ref>PMID:11734221</ref> <ref>PMID:12019181</ref> <ref>PMID:11997495</ref> <ref>PMID:15147734</ref> <ref>PMID:15486195</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==

6tqq

From Proteopedia

Revision as of 15:19, 8 June 2021

Structural insight into tanapoxvirus mediated inhibition of apoptosis

Structural highlights

Function

Publication Abstract from PubMed

References

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