3fke - Revision history

OCA at 09:49, 21 February 2024

OCA — Wed, 21 Feb 2024 09:49:43 GMT

←Older revision		Revision as of 09:49, 21 February 2024
Line 9:		Line 9:
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/VP35_EBOZM VP35_EBOZM] Acsts as a polymerase cofactor in the RNA polymerase transcription and replication complex. Prevents establishment of cellular antiviral state by blocking virus-induced phosphorylation and activation of interferon regulatory factor 3 (IRF3), a transcription factor critical for the induction of interferons alpha and beta. The mechanism by which this blockage occurs remains incompletely defined, a hypothesis suggests that VP35 dsRNA-binding activity prevents activation of IRF3 by sequestering dsRNA. Also inhibits the antiviral effect mediated by the interferon-induced, double-stranded RNA-activated protein kinase EIF2AK2/PKR.<ref>PMID:9971816</ref> <ref>PMID:11027311</ref> <ref>PMID:12829834</ref> <ref>PMID:16495261</ref> <ref>PMID:17065211</ref>		[https://www.uniprot.org/uniprot/VP35_EBOZM VP35_EBOZM] Acsts as a polymerase cofactor in the RNA polymerase transcription and replication complex. Prevents establishment of cellular antiviral state by blocking virus-induced phosphorylation and activation of interferon regulatory factor 3 (IRF3), a transcription factor critical for the induction of interferons alpha and beta. The mechanism by which this blockage occurs remains incompletely defined, a hypothesis suggests that VP35 dsRNA-binding activity prevents activation of IRF3 by sequestering dsRNA. Also inhibits the antiviral effect mediated by the interferon-induced, double-stranded RNA-activated protein kinase EIF2AK2/PKR.<ref>PMID:9971816</ref> <ref>PMID:11027311</ref> <ref>PMID:12829834</ref> <ref>PMID:16495261</ref> <ref>PMID:17065211</ref>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	Ebola viruses (EBOVs) cause rare but highly fatal outbreaks of viral hemorrhagic fever in humans, and approved treatments for these infections are currently lacking. The Ebola VP35 protein is multifunctional, acting as a component of the viral RNA polymerase complex, a viral assembly factor, and an inhibitor of host interferon (IFN) production. Mutation of select basic residues within the C-terminal half of VP35 abrogates its dsRNA-binding activity, impairs VP35-mediated IFN antagonism, and attenuates EBOV growth in vitro and in vivo. Because VP35 contributes to viral escape from host innate immunity and is required for EBOV virulence, understanding the structural basis for VP35 dsRNA binding, which correlates with suppression of IFN activity, is of high importance. Here, we report the structure of the C-terminal VP35 IFN inhibitory domain (IID) solved to a resolution of 1.4 A and show that VP35 IID forms a unique fold. In the structure, we identify 2 basic residue clusters, one of which is important for dsRNA binding. The dsRNA binding cluster is centered on Arg-312, a highly conserved residue required for IFN inhibition. Mutation of residues within this cluster significantly changes the surface electrostatic potential and diminishes dsRNA binding activity. The high-resolution structure and the identification of the conserved dsRNA binding residue cluster provide opportunities for antiviral therapeutic design. Our results suggest a structure-based model for dsRNA-mediated innate immune antagonism by Ebola VP35 and other similarly constructed viral antagonists.
-
-	Structure of the Ebola VP35 interferon inhibitory domain.,Leung DW, Ginder ND, Fulton DB, Nix J, Basler CF, Honzatko RB, Amarasinghe GK Proc Natl Acad Sci U S A. 2009 Jan 2. PMID:19122151<ref>PMID:19122151</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 3fke" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 09:33, 6 December 2023

OCA — Wed, 06 Dec 2023 09:33:24 GMT

←Older revision		Revision as of 09:33, 6 December 2023
Line 3:		Line 3:
	<StructureSection load='3fke' size='340' side='right'caption='[[3fke]], [[Resolution\|resolution]] 1.40Å' scene=''>		<StructureSection load='3fke' size='340' side='right'caption='[[3fke]], [[Resolution\|resolution]] 1.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3fke]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Ebov~~-~~may Ebov~~-~~may~~]. The October 2014 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Ebola Virus Proteins'' by David Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2014_10 10.2210/rcsb_pdb/mom_2014_10]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FKE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3FKE FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3fke]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Ebola_virus_-_Mayinga,_Zaire,_1976 Ebola virus - Mayinga, Zaire, 1976]. The October 2014 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Ebola Virus Proteins'' by David Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2014_10 10.2210/rcsb_pdb/mom_2014_10]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FKE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3FKE FirstGlance]. <br>
-	</td></tr><tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat">~~VP35 (~~[~~https://www~~.~~ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info~~&~~srchmode=5&id=128952 EBOV-May])~~</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]] 1.4Å</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=3fke FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fke OCA], [https://pdbe.org/3fke PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3fke RCSB], [https://www.ebi.ac.uk/pdbsum/3fke PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3fke 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=3fke FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fke OCA], [https://pdbe.org/3fke PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3fke RCSB], [https://www.ebi.ac.uk/pdbsum/3fke PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3fke ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/VP35_EBOZM VP35_EBOZM]] Acsts as a polymerase cofactor in the RNA polymerase transcription and replication complex. Prevents establishment of cellular antiviral state by blocking virus-induced phosphorylation and activation of interferon regulatory factor 3 (IRF3), a transcription factor critical for the induction of interferons alpha and beta. The mechanism by which this blockage occurs remains incompletely defined, a hypothesis suggests that VP35 dsRNA-binding activity prevents activation of IRF3 by sequestering dsRNA. Also inhibits the antiviral effect mediated by the interferon-induced, double-stranded RNA-activated protein kinase EIF2AK2/PKR.<ref>PMID:9971816</ref> <ref>PMID:11027311</ref> <ref>PMID:12829834</ref> <ref>PMID:16495261</ref> <ref>PMID:17065211</ref>	+	[https://www.uniprot.org/uniprot/VP35_EBOZM VP35_EBOZM] Acsts as a polymerase cofactor in the RNA polymerase transcription and replication complex. Prevents establishment of cellular antiviral state by blocking virus-induced phosphorylation and activation of interferon regulatory factor 3 (IRF3), a transcription factor critical for the induction of interferons alpha and beta. The mechanism by which this blockage occurs remains incompletely defined, a hypothesis suggests that VP35 dsRNA-binding activity prevents activation of IRF3 by sequestering dsRNA. Also inhibits the antiviral effect mediated by the interferon-induced, double-stranded RNA-activated protein kinase EIF2AK2/PKR.<ref>PMID:9971816</ref> <ref>PMID:11027311</ref> <ref>PMID:12829834</ref> <ref>PMID:16495261</ref> <ref>PMID:17065211</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</StructureSection>		</StructureSection>
	[[Category: Ebola Virus Proteins]]		[[Category: Ebola Virus Proteins]]
-	[[Category: ~~Ebov~~-~~may~~]]	+	[[Category: Ebola virus - Mayinga, Zaire, 1976]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: RCSB PDB Molecule of the Month]]		[[Category: RCSB PDB Molecule of the Month]]
-	[[Category: Amarasinghe~~, G K~~]]	+	[[Category: Amarasinghe GK]]
-	[[Category: Basler~~, C F~~]]	+	[[Category: Basler CF]]
-	[[Category: Fulton~~, D B~~]]	+	[[Category: Fulton DB]]
-	[[Category: Ginder~~, N D~~]]	+	[[Category: Ginder ND]]
-	[[Category: Honzatko~~, R B~~]]	+	[[Category: Honzatko RB]]
-	[[Category: Leung~~, D W~~]]	+	[[Category: Leung DW]]
-	[[Category: Nix, J]]	+	[[Category: Nix J]]
-	~~[[Category: Coiled coil]]~~	+
-	~~[[Category: Interferon antiviral system evasion]]~~	+
-	~~[[Category: Rna binding domain]]~~	+
-	~~[[Category: Rna binding protein]]~~	+
-	~~[[Category: Rna replication]]~~	+
-	~~[[Category: Rna-binding]]~~	+
-	~~[[Category: Transcription~~]]	+

OCA at 08:03, 2 March 2022

OCA — Wed, 02 Mar 2022 08:03:20 GMT

←Older revision		Revision as of 08:03, 2 March 2022
Line 1:		Line 1:

	==Structure of the Ebola VP35 Interferon Inhibitory Domain==		==Structure of the Ebola VP35 Interferon Inhibitory Domain==
-	<StructureSection load='3fke' size='340' side='right' caption='[[3fke]], [[Resolution\|resolution]] 1.40Å' scene=''>	+	<StructureSection load='3fke' size='340' side='right'caption='[[3fke]], [[Resolution\|resolution]] 1.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3fke]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Ebov-may Ebov-may]. The October 2014 RCSB PDB [~~http~~://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Ebola Virus Proteins'' by David Goodsell is [~~http~~://dx.doi.org/10.2210/rcsb_pdb/mom_2014_10 10.2210/rcsb_pdb/mom_2014_10]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FKE OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3FKE FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3fke]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Ebov-may Ebov-may]. The October 2014 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Ebola Virus Proteins'' by David Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2014_10 10.2210/rcsb_pdb/mom_2014_10]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FKE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3FKE FirstGlance]. <br>
-	</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">VP35 ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=128952 EBOV-May])</td></tr>	+	</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">VP35 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=128952 EBOV-May])</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=3fke FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fke OCA], [~~http~~://pdbe.org/3fke PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3fke RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3fke PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3fke 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=3fke FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fke OCA], [https://pdbe.org/3fke PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3fke RCSB], [https://www.ebi.ac.uk/pdbsum/3fke PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3fke ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/VP35_EBOZM VP35_EBOZM]] Acsts as a polymerase cofactor in the RNA polymerase transcription and replication complex. Prevents establishment of cellular antiviral state by blocking virus-induced phosphorylation and activation of interferon regulatory factor 3 (IRF3), a transcription factor critical for the induction of interferons alpha and beta. The mechanism by which this blockage occurs remains incompletely defined, a hypothesis suggests that VP35 dsRNA-binding activity prevents activation of IRF3 by sequestering dsRNA. Also inhibits the antiviral effect mediated by the interferon-induced, double-stranded RNA-activated protein kinase EIF2AK2/PKR.<ref>PMID:9971816</ref> <ref>PMID:11027311</ref> <ref>PMID:12829834</ref> <ref>PMID:16495261</ref> <ref>PMID:17065211</ref>	+	[[https://www.uniprot.org/uniprot/VP35_EBOZM VP35_EBOZM]] Acsts as a polymerase cofactor in the RNA polymerase transcription and replication complex. Prevents establishment of cellular antiviral state by blocking virus-induced phosphorylation and activation of interferon regulatory factor 3 (IRF3), a transcription factor critical for the induction of interferons alpha and beta. The mechanism by which this blockage occurs remains incompletely defined, a hypothesis suggests that VP35 dsRNA-binding activity prevents activation of IRF3 by sequestering dsRNA. Also inhibits the antiviral effect mediated by the interferon-induced, double-stranded RNA-activated protein kinase EIF2AK2/PKR.<ref>PMID:9971816</ref> <ref>PMID:11027311</ref> <ref>PMID:12829834</ref> <ref>PMID:16495261</ref> <ref>PMID:17065211</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 24:		Line 24:
	[[Category: Ebola Virus Proteins]]		[[Category: Ebola Virus Proteins]]
	[[Category: Ebov-may]]		[[Category: Ebov-may]]
		+	[[Category: Large Structures]]
	[[Category: RCSB PDB Molecule of the Month]]		[[Category: RCSB PDB Molecule of the Month]]
	[[Category: Amarasinghe, G K]]		[[Category: Amarasinghe, G K]]

OCA at 07:19, 5 December 2018

OCA — Wed, 05 Dec 2018 07:19:29 GMT

←Older revision		Revision as of 07:19, 5 December 2018
Line 3:		Line 3:
	<StructureSection load='3fke' size='340' side='right' caption='[[3fke]], [[Resolution\|resolution]] 1.40Å' scene=''>		<StructureSection load='3fke' size='340' side='right' caption='[[3fke]], [[Resolution\|resolution]] 1.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3fke]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Ebozm Ebozm~~]. The October 2014 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Ebola Virus Proteins'' by David Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2014_10 10.2210/rcsb_pdb/mom_2014_10]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FKE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3FKE FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3fke]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Ebov-may Ebov-may]. The October 2014 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Ebola Virus Proteins'' by David Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2014_10 10.2210/rcsb_pdb/mom_2014_10]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FKE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3FKE FirstGlance]. <br>
-	</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">VP35 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=128952 ~~EBOZM~~])</td></tr>	+	</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">VP35 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=128952 EBOV-May])</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=3fke FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fke OCA], [http://pdbe.org/3fke PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3fke RCSB], [http://www.ebi.ac.uk/pdbsum/3fke PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3fke 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=3fke FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fke OCA], [http://pdbe.org/3fke PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3fke RCSB], [http://www.ebi.ac.uk/pdbsum/3fke PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3fke ProSAT]</span></td></tr>
	</table>		</table>
Line 23:		Line 23:
	</StructureSection>		</StructureSection>
	[[Category: Ebola Virus Proteins]]		[[Category: Ebola Virus Proteins]]
-	[[Category: ~~Ebozm~~]]	+	[[Category: Ebov-may]]
	[[Category: RCSB PDB Molecule of the Month]]		[[Category: RCSB PDB Molecule of the Month]]
	[[Category: Amarasinghe, G K]]		[[Category: Amarasinghe, G K]]
Line 32:		Line 32:
	[[Category: Leung, D W]]		[[Category: Leung, D W]]
	[[Category: Nix, J]]		[[Category: Nix, J]]
		+	[[Category: Coiled coil]]
	[[Category: Interferon antiviral system evasion]]		[[Category: Interferon antiviral system evasion]]
	[[Category: Rna binding domain]]		[[Category: Rna binding domain]]

OCA at 08:32, 4 August 2016

OCA — Thu, 04 Aug 2016 08:32:32 GMT

←Older revision		Revision as of 08:32, 4 August 2016
Line 1:		Line 1:
		+
	==Structure of the Ebola VP35 Interferon Inhibitory Domain==		==Structure of the Ebola VP35 Interferon Inhibitory Domain==
	<StructureSection load='3fke' size='340' side='right' caption='[[3fke]], [[Resolution\|resolution]] 1.40Å' scene=''>		<StructureSection load='3fke' size='340' side='right' caption='[[3fke]], [[Resolution\|resolution]] 1.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3fke]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Viruses Viruses~~]. The October 2014 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Ebola Virus Proteins'' by David Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2014_10 10.2210/rcsb_pdb/mom_2014_10]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FKE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3FKE FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3fke]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Ebozm Ebozm]. The October 2014 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Ebola Virus Proteins'' by David Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2014_10 10.2210/rcsb_pdb/mom_2014_10]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FKE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3FKE FirstGlance]. <br>
-	</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">VP35 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=~~10239 Viruses~~])</td></tr>	+	</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">VP35 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=128952 EBOZM])</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=3fke FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fke OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3fke RCSB], [http://www.ebi.ac.uk/pdbsum/3fke PDBsum]</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=3fke FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fke OCA], [http://pdbe.org/3fke PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3fke RCSB], [http://www.ebi.ac.uk/pdbsum/3fke PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3fke ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 16:		Line 17:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 3fke" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
Line 21:		Line 23:
	</StructureSection>		</StructureSection>
	[[Category: Ebola Virus Proteins]]		[[Category: Ebola Virus Proteins]]
		+	[[Category: Ebozm]]
	[[Category: RCSB PDB Molecule of the Month]]		[[Category: RCSB PDB Molecule of the Month]]
-	[[Category: Viruses]]
	[[Category: Amarasinghe, G K]]		[[Category: Amarasinghe, G K]]
	[[Category: Basler, C F]]		[[Category: Basler, C F]]

OCA at 07:43, 24 December 2014

OCA — Wed, 24 Dec 2014 07:43:18 GMT

←Older revision		Revision as of 07:43, 24 December 2014
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	<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=3fke FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fke OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3fke RCSB], [http://www.ebi.ac.uk/pdbsum/3fke PDBsum]</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=3fke FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fke OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3fke RCSB], [http://www.ebi.ac.uk/pdbsum/3fke PDBsum]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/VP35_EBOZM VP35_EBOZM]] Acsts as a polymerase cofactor in the RNA polymerase transcription and replication complex. Prevents establishment of cellular antiviral state by blocking virus-induced phosphorylation and activation of interferon regulatory factor 3 (IRF3), a transcription factor critical for the induction of interferons alpha and beta. The mechanism by which this blockage occurs remains incompletely defined, a hypothesis suggests that VP35 dsRNA-binding activity prevents activation of IRF3 by sequestering dsRNA. Also inhibits the antiviral effect mediated by the interferon-induced, double-stranded RNA-activated protein kinase EIF2AK2/PKR.<ref>PMID:9971816</ref> <ref>PMID:11027311</ref> <ref>PMID:12829834</ref> <ref>PMID:16495261</ref> <ref>PMID:17065211</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 10:08, 3 December 2014

OCA — Wed, 03 Dec 2014 10:08:05 GMT

←Older revision		Revision as of 10:08, 3 December 2014
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-	[[~~Image:~~3fke.~~png~~\|~~left\|200px~~]]	+	==Structure of the Ebola VP35 Interferon Inhibitory Domain==
		+	<StructureSection load='3fke' size='340' side='right' caption='[[3fke]], [[Resolution\|resolution]] 1.40Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[3fke]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Viruses Viruses]. The October 2014 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Ebola Virus Proteins'' by David Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2014_10 10.2210/rcsb_pdb/mom_2014_10]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FKE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3FKE FirstGlance]. <br>
		+	</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">VP35 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10239 Viruses])</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=3fke FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fke OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3fke RCSB], [http://www.ebi.ac.uk/pdbsum/3fke PDBsum]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Ebola viruses (EBOVs) cause rare but highly fatal outbreaks of viral hemorrhagic fever in humans, and approved treatments for these infections are currently lacking. The Ebola VP35 protein is multifunctional, acting as a component of the viral RNA polymerase complex, a viral assembly factor, and an inhibitor of host interferon (IFN) production. Mutation of select basic residues within the C-terminal half of VP35 abrogates its dsRNA-binding activity, impairs VP35-mediated IFN antagonism, and attenuates EBOV growth in vitro and in vivo. Because VP35 contributes to viral escape from host innate immunity and is required for EBOV virulence, understanding the structural basis for VP35 dsRNA binding, which correlates with suppression of IFN activity, is of high importance. Here, we report the structure of the C-terminal VP35 IFN inhibitory domain (IID) solved to a resolution of 1.4 A and show that VP35 IID forms a unique fold. In the structure, we identify 2 basic residue clusters, one of which is important for dsRNA binding. The dsRNA binding cluster is centered on Arg-312, a highly conserved residue required for IFN inhibition. Mutation of residues within this cluster significantly changes the surface electrostatic potential and diminishes dsRNA binding activity. The high-resolution structure and the identification of the conserved dsRNA binding residue cluster provide opportunities for antiviral therapeutic design. Our results suggest a structure-based model for dsRNA-mediated innate immune antagonism by Ebola VP35 and other similarly constructed viral antagonists.

-	~~{{STRUCTURE_3fke\| PDB=3fke \| SCENE= }}~~	+	Structure of the Ebola VP35 interferon inhibitory domain.,Leung DW, Ginder ND, Fulton DB, Nix J, Basler CF, Honzatko RB, Amarasinghe GK Proc Natl Acad Sci U S A. 2009 Jan 2. PMID:19122151<ref>PMID:19122151</ref>

-	~~===Structure~~ of the ~~Ebola VP35 Interferon Inhibitory Domain===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~{{ABSTRACT_PUBMED_19122151}}~~	+	== References ==
-		+	<references/>
-	~~==About this Structure==~~	+	__TOC__
-	~~[[3fke]] is a 2 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Viruses Viruses]~~. ~~Full crystallographic information is available from [http:~~/~~/oca.weizmann.ac.il/oca-bin/ocashort?id=3FKE OCA].~~	+	</StructureSection>
-		+	[[Category: Ebola Virus Proteins]]
-	==~~Reference~~==	+	[[Category: RCSB PDB Molecule of the Month]]
-	<~~ref group="xtra">PMID:019122151<~~/~~ref~~><~~references group="xtra"~~/>	+
	[[Category: Viruses]]		[[Category: Viruses]]
-	[[Category: Amarasinghe, G K.]]	+	[[Category: Amarasinghe, G K]]
-	[[Category: Basler, C F.]]	+	[[Category: Basler, C F]]
-	[[Category: Fulton, D B.]]	+	[[Category: Fulton, D B]]
-	[[Category: Ginder, N D.]]	+	[[Category: Ginder, N D]]
-	[[Category: Honzatko, R B.]]	+	[[Category: Honzatko, R B]]
-	[[Category: Leung, D W.]]	+	[[Category: Leung, D W]]
-	[[Category: Nix, J.]]	+	[[Category: Nix, J]]
	[[Category: Interferon antiviral system evasion]]		[[Category: Interferon antiviral system evasion]]
	[[Category: Rna binding domain]]		[[Category: Rna binding domain]]

OCA: Protected "3fke" [edit=sysop:move=sysop]

OCA — Wed, 13 Feb 2013 10:56:24 GMT

Protected "3fke" [edit=sysop:move=sysop]

←Older revision

Revision as of 10:56, 13 February 2013

OCA at 10:56, 13 February 2013

OCA — Wed, 13 Feb 2013 10:56:22 GMT

←Older revision		Revision as of 10:56, 13 February 2013
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-	{{Seed}}
	[[Image:3fke.png\|left\|200px]]		[[Image:3fke.png\|left\|200px]]

-	<!--
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	{{STRUCTURE_3fke\| PDB=3fke \| SCENE= }}		{{STRUCTURE_3fke\| PDB=3fke \| SCENE= }}

	===Structure of the Ebola VP35 Interferon Inhibitory Domain===		===Structure of the Ebola VP35 Interferon Inhibitory Domain===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_19122151}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 19122151 is the PubMed ID number.
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	{{ABSTRACT_PUBMED_19122151}}		{{ABSTRACT_PUBMED_19122151}}

	==About this Structure==		==About this Structure==
-	~~3FKE~~ is a 2 ~~chains~~ structure ~~of sequences~~ from [http://en.wikipedia.org/wiki/Viruses Viruses]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FKE OCA].	+	[[3fke]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Viruses Viruses]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FKE OCA].

	==Reference==		==Reference==
-	<ref group="xtra">PMID:~~19122151~~</ref><references group="xtra"/>	+	<ref group="xtra">PMID:019122151</ref><references group="xtra"/>
	[[Category: Viruses]]		[[Category: Viruses]]
	[[Category: Amarasinghe, G K.]]		[[Category: Amarasinghe, G K.]]
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	[[Category: Leung, D W.]]		[[Category: Leung, D W.]]
	[[Category: Nix, J.]]		[[Category: Nix, J.]]
-	[[Category: Coiled coil]]
	[[Category: Interferon antiviral system evasion]]		[[Category: Interferon antiviral system evasion]]
	[[Category: Rna binding domain]]		[[Category: Rna binding domain]]
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	[[Category: Rna-binding]]		[[Category: Rna-binding]]
	[[Category: Transcription]]		[[Category: Transcription]]
-
-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb 15 08:48:37 2009''

OCA at 06:48, 15 February 2009

OCA — Sun, 15 Feb 2009 06:48:37 GMT

←Older revision		Revision as of 06:48, 15 February 2009
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	==About this Structure==		==About this Structure==
-	3FKE is a ~~[[Single protein]]~~ structure of ~~sequence~~ from [http://en.wikipedia.org/wiki/Viruses Viruses]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FKE OCA].	+	3FKE is a 2 chains structure of sequences from [http://en.wikipedia.org/wiki/Viruses Viruses]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FKE OCA].

	==Reference==		==Reference==
-	~~Structure of the Ebola VP35 interferon inhibitory domain., Leung DW, Ginder ND, Fulton DB, Nix J, Basler CF, Honzatko RB, Amarasinghe GK, Proc Natl Acad Sci U S A. 2009 Jan 2.~~ PMID:~~[http:~~//~~www.ncbi.nlm.nih.gov/pubmed/19122151 19122151]~~	+	<ref group="xtra">PMID:19122151</ref><references group="xtra"/>
-	~~[[Category: Single protein]]~~	+
	[[Category: Viruses]]		[[Category: Viruses]]
-	[[Category: ~~Pdbx_ordinal=~~, ~~<PDBx~~:~~audit_author~~.]]	+	[[Category: Amarasinghe, G K.]]
		+	[[Category: Basler, C F.]]
		+	[[Category: Fulton, D B.]]
		+	[[Category: Ginder, N D.]]
		+	[[Category: Honzatko, R B.]]
		+	[[Category: Leung, D W.]]
		+	[[Category: Nix, J.]]
	[[Category: Coiled coil]]		[[Category: Coiled coil]]
	[[Category: Interferon antiviral system evasion]]		[[Category: Interferon antiviral system evasion]]
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	[[Category: Transcription]]		[[Category: Transcription]]

-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Wed~~ Feb ~~11 20~~:09:41 2009''	+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb 15 08:48:37 2009''