5wos: Difference between revisions

Revision as of 10:00, 1 January 2020

Structural and functional insights into Canarypox Virus CNP058 regulation of apoptosis

Structural highlights

5wos is a 2 chain structure with sequence from Avipoxvirus clade b1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	CNPV058 (Avipoxvirus clade B1)
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

Programmed cell death or apoptosis is an important component of host defense systems against viral infection. The B-cell lymphoma 2 (Bcl-2) proteins family is the main arbiter of mitochondrially mediated apoptosis, and viruses have evolved sequence and structural mimics of Bcl-2 to subvert premature host cell apoptosis in response to viral infection. The sequencing of the canarypox virus genome identified a putative pro-survival Bcl-2 protein, CNP058. However, a role in apoptosis inhibition for CNP058 has not been identified to date. Here, we report that CNP058 is able to bind several host cell pro-death Bcl-2 proteins, including Bak and Bax, as well as several BH3 only-proteins including Bim, Bid, Bmf, Noxa, Puma, and Hrk with high to moderate affinities. We then defined the structural basis for CNP058 binding to pro-death Bcl-2 proteins by determining the crystal structure of CNP058 bound to Bim BH3. CNP058 adopts the conserved Bcl-2 like fold observed in cellular pro-survival Bcl-2 proteins, and utilizes the canonical ligand binding groove to bind Bim BH3. We then demonstrate that CNP058 is a potent inhibitor of ultraviolet (UV) induced apoptosis in a cell culture model. Our findings suggest that CNP058 is a potent inhibitor of apoptosis that is able to bind to BH3 domain peptides from a broad range of pro-death Bcl-2 proteins, and may play a key role in countering premature host apoptosis.

Structural and Functional Insight into Canarypox Virus CNP058 Mediated Regulation of Apoptosis.,Anasir MI, Baxter AA, Poon IKH, Hulett MD, Kvansakul M Viruses. 2017 Oct 20;9(10). pii: E305. doi: 10.3390/v9100305. PMID:29053589^[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:https://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:https://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
↑ Anasir MI, Baxter AA, Poon IKH, Hulett MD, Kvansakul M. Structural and Functional Insight into Canarypox Virus CNP058 Mediated Regulation of Apoptosis. Viruses. 2017 Oct 20;9(10). pii: E305. doi: 10.3390/v9100305. PMID:29053589 doi:https://dx.doi.org/10.3390/v9100305

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OCA

[1] 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:https://dx.doi.org/10.1093/emboj/17.2.384

[2] 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

[3] 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

[4] 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

[5] 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:https://dx.doi.org/10.1016/j.biocel.2003.12.015

[6] 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

[7] Anasir MI, Baxter AA, Poon IKH, Hulett MD, Kvansakul M. Structural and Functional Insight into Canarypox Virus CNP058 Mediated Regulation of Apoptosis. Viruses. 2017 Oct 20;9(10). pii: E305. doi: 10.3390/v9100305. PMID:29053589 doi:https://dx.doi.org/10.3390/v9100305

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@@ Line 1: / Line 1: @@
 ==Structural and functional insights into Canarypox Virus CNP058 regulation of apoptosis==
-<StructureSection load='5wos' size='340' side='right' caption='[[5wos]], [[Resolution|resolution]] 2.45&Aring;' scene=''>
+<StructureSection load='5wos' size='340' side='right'caption='[[5wos]], [[Resolution|resolution]] 2.45&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5wos]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WOS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WOS FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5wos]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Avipoxvirus_clade_b1 Avipoxvirus clade b1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WOS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WOS FirstGlance]. <br>
-</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=5wos FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wos OCA], [http://pdbe.org/5wos PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wos RCSB], [http://www.ebi.ac.uk/pdbsum/5wos PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wos ProSAT]</span></td></tr>
+</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CNPV058 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=44088 Avipoxvirus clade B1])</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=5wos FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wos OCA], [http://pdbe.org/5wos PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wos RCSB], [http://www.ebi.ac.uk/pdbsum/5wos PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wos ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 17: / Line 18: @@
 </div>
 <div class="pdbe-citations 5wos" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[B-cell lymphoma proteins 3D structures|B-cell lymphoma proteins 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Avipoxvirus clade b1]]
+[[Category: Large Structures]]
 [[Category: Anasir, M I]]
 [[Category: Kvansakul, M]]

5wos: Difference between revisions

Revision as of 10:00, 1 January 2020

Structural and functional insights into Canarypox Virus CNP058 regulation of apoptosis

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

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