6xdc - Revision history

OCA at 19:42, 7 September 2022

2022-09-07T19:42:36Z

←Older revision		Revision as of 19:42, 7 September 2022
Line 3:		Line 3:
	<StructureSection load='6xdc' size='340' side='right'caption='[[6xdc]], [[Resolution\|resolution]] 2.90Å' scene=''>		<StructureSection load='6xdc' size='340' side='right'caption='[[6xdc]], [[Resolution\|resolution]] 2.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6xdc]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6XDC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6XDC FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6xdc]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Severe_acute_respiratory_syndrome_coronavirus_2 Severe acute respiratory syndrome coronavirus 2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6XDC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6XDC FirstGlance]. <br>
	</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=6xdc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xdc OCA], [https://pdbe.org/6xdc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6xdc RCSB], [https://www.ebi.ac.uk/pdbsum/6xdc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6xdc ProSAT]</span></td></tr>		</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=6xdc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xdc OCA], [https://pdbe.org/6xdc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6xdc RCSB], [https://www.ebi.ac.uk/pdbsum/6xdc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6xdc ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/AP3A_SARS2 AP3A_SARS2]] Forms homotetrameric potassium sensitive ion channels (viroporin) and may modulate virus release. Up-regulates expression of fibrinogen subunits FGA, FGB and FGG in host lung epithelial cells. Induces apoptosis in cell culture. Downregulates the type 1 interferon receptor by inducing serine phosphorylation within the IFN alpha-receptor subunit 1 (IFNAR1) degradation motif and increasing IFNAR1 ubiquitination.[UniProtKB:P59632]	+	[[https://www.uniprot.org/uniprot/AP3A_SARS2 AP3A_SARS2]] Forms homotetrameric potassium sensitive ion channels (viroporin) and may modulate virus release. Up-regulates expression of fibrinogen subunits FGA, FGB and FGG in host lung epithelial cells. Induces apoptosis in cell culture. Downregulates the type 1 interferon receptor by inducing serine phosphorylation within the IFN alpha-receptor subunit 1 (IFNAR1) degradation motif and increasing IFNAR1 ubiquitination.[UniProtKB:P59632]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 22:		Line 22:
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Brohawn, S G~~]]	+	[[Category: Severe acute respiratory syndrome coronavirus 2]]
-	[[Category: ~~Hoel, C M~~]]	+	[[Category: Brohawn SG]]
-	[[Category: ~~Kern, D M~~]]	+	[[Category: Hoel CM]]
-	[[Category: ~~Coronavirus]]~~	+	[[Category: Kern DM]]
-	~~[[Category: Ion channel]]~~	+
-	~~[[Category: Sars-cov-2]]~~	+
-	~~[[Category: Transport protein]]~~	+
-	~~[[Category: Viroporin~~]]	+

OCA at 06:41, 31 August 2022

2022-08-31T06:41:17Z

←Older revision		Revision as of 06:41, 31 August 2022
Line 1:		Line 1:

	==Cryo-EM structure of SARS-CoV-2 ORF3a==		==Cryo-EM structure of SARS-CoV-2 ORF3a==
-	<StructureSection load='6xdc' size='340' side='right'caption='[[6xdc]]' scene=''>	+	<StructureSection load='6xdc' size='340' side='right'caption='[[6xdc]], [[Resolution\|resolution]] 2.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6XDC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6XDC FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6xdc]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6XDC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6XDC FirstGlance]. <br>
	</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=6xdc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xdc OCA], [https://pdbe.org/6xdc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6xdc RCSB], [https://www.ebi.ac.uk/pdbsum/6xdc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6xdc ProSAT]</span></td></tr>		</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=6xdc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xdc OCA], [https://pdbe.org/6xdc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6xdc RCSB], [https://www.ebi.ac.uk/pdbsum/6xdc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6xdc ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/AP3A_SARS2 AP3A_SARS2]] Forms homotetrameric potassium sensitive ion channels (viroporin) and may modulate virus release. Up-regulates expression of fibrinogen subunits FGA, FGB and FGG in host lung epithelial cells. Induces apoptosis in cell culture. Downregulates the type 1 interferon receptor by inducing serine phosphorylation within the IFN alpha-receptor subunit 1 (IFNAR1) degradation motif and increasing IFNAR1 ubiquitination.[UniProtKB:P59632]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	SARS-CoV-2 ORF3a is a putative viral ion channel implicated in autophagy inhibition, inflammasome activation and apoptosis. 3a protein and anti-3a antibodies are found in infected patient tissues and plasma. Deletion of 3a in SARS-CoV-1 reduces viral titer and morbidity in mice, suggesting it could be an effective target for vaccines or therapeutics. Here, we present structures of SARS-CoV-2 3a determined by cryo-EM to 2.1-A resolution. 3a adopts a new fold with a polar cavity that opens to the cytosol and membrane through separate water- and lipid-filled openings. Hydrophilic grooves along outer helices could form ion-conduction paths. Using electrophysiology and fluorescent ion imaging of 3a-reconstituted liposomes, we observe Ca(2+)-permeable, nonselective cation channel activity, identify mutations that alter ion permeability and discover polycationic inhibitors of 3a activity. 3a-like proteins are found across coronavirus lineages that infect bats and humans, suggesting that 3a-targeted approaches could treat COVID-19 and other coronavirus diseases.
		+
		+	Cryo-EM structure of SARS-CoV-2 ORF3a in lipid nanodiscs.,Kern DM, Sorum B, Mali SS, Hoel CM, Sridharan S, Remis JP, Toso DB, Kotecha A, Bautista DM, Brohawn SG Nat Struct Mol Biol. 2021 Jul;28(7):573-582. doi: 10.1038/s41594-021-00619-0., Epub 2021 Jun 22. PMID:34158638<ref>PMID:34158638</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6xdc" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Brohawn SG]]	+	[[Category: Brohawn, S G]]
-	[[Category: Hoel CM]]	+	[[Category: Hoel, C M]]
-	[[Category: Kern DM]]	+	[[Category: Kern, D M]]
		+	[[Category: Coronavirus]]
		+	[[Category: Ion channel]]
		+	[[Category: Sars-cov-2]]
		+	[[Category: Transport protein]]
		+	[[Category: Viroporin]]

OCA at 06:14, 18 August 2021

2021-08-18T06:14:34Z

←Older revision		Revision as of 06:14, 18 August 2021
Line 1:		Line 1:

	==Cryo-EM structure of SARS-CoV-2 ORF3a==		==Cryo-EM structure of SARS-CoV-2 ORF3a==
-	<StructureSection load='6xdc' size='340' side='right'caption='[[6xdc]]~~, [[Resolution\|resolution]] 2.90Å~~' scene=''>	+	<StructureSection load='6xdc' size='340' side='right'caption='[[6xdc]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>~~[[6xdc]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/2019-ncov 2019-ncov].~~ Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6XDC OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6XDC FirstGlance]. <br>	+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6XDC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6XDC FirstGlance]. <br>
-	</td></tr>~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">3a ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=2697049 2019-nCoV])</td></tr>~~	+	</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=6xdc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xdc OCA], [https://pdbe.org/6xdc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6xdc RCSB], [https://www.ebi.ac.uk/pdbsum/6xdc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6xdc ProSAT]</span></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=6xdc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xdc OCA], [~~http~~://pdbe.org/6xdc PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6xdc RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6xdc PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6xdc ProSAT]</span></td></tr>	+
	</table>		</table>
-	== Function ==
-	[[http://www.uniprot.org/uniprot/AP3A_SARS2 AP3A_SARS2]] Forms homotetrameric potassium sensitive ion channels (viroporin) and may modulate virus release. Up-regulates expression of fibrinogen subunits FGA, FGB and FGG in host lung epithelial cells. Induces apoptosis in cell culture. Downregulates the type 1 interferon receptor by inducing serine phosphorylation within the IFN alpha-receptor subunit 1 (IFNAR1) degradation motif and increasing IFNAR1 ubiquitination.[UniProtKB:P59632]
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	SARS-CoV-2 encodes three putative ion channels: E, 8a, and 3a. In related SARS-CoV-1, 3a is implicated in viral release, inflammasome activation, and cell death and its deletion reduces viral titer and morbidity in animal models, suggesting 3a-targeted therapeutics could treat SARS and COVID-19. However, the structural basis for the function of 3a is unknown. Here, we show that SARS-CoV-2 forms large conductance cation channels and present cryo-EM structures of dimeric and tetrameric SARS-CoV-2 3a in lipid nanodiscs. 3a adopts a novel fold and is captured in a closed or inactivated state. A narrow bifurcated exterior pore precludes conduction and leads to a large polar cavity open to the cytosol. 3a function is conserved in a common variant among circulating SARS-CoV-2 that alters the channel pore. We identify 3a-like proteins in Alpha- and Beta-coronaviruses that infect bats and humans, suggesting therapeutics targeting 3a could treat a range of coronaviral diseases.
-
-	Cryo-EM structure of the SARS-CoV-2 3a ion channel in lipid nanodiscs.,Kern DM, Sorum B, Hoel CM, Sridharan S, Remis JP, Toso DB, Brohawn SG bioRxiv. 2020 Jun 18. doi: 10.1101/2020.06.17.156554. PMID:32587976<ref>PMID:32587976</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 6xdc" style="background-color:#fffaf0;"></div>
-	== References ==
-	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: 2019-ncov]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Brohawn~~, S G~~]]	+	[[Category: Brohawn SG]]
-	[[Category: Hoel~~, C M~~]]	+	[[Category: Hoel CM]]
-	[[Category: Kern~~, D M]]~~	+	[[Category: Kern DM]]
-	~~[[Category: Coronavirus]]~~	+
-	~~[[Category: Ion channel]]~~	+
-	~~[[Category: Sars-cov-2]]~~	+
-	~~[[Category: Transport protein]]~~	+
-	~~[[Category: Viroporin~~]]	+

OCA at 14:42, 8 July 2020

2020-07-08T14:42:40Z

←Older revision		Revision as of 14:42, 8 July 2020
Line 1:		Line 1:

	==Cryo-EM structure of SARS-CoV-2 ORF3a==		==Cryo-EM structure of SARS-CoV-2 ORF3a==
-	<StructureSection load='6xdc' size='340' side='right'caption='[[6xdc]]' scene=''>	+	<StructureSection load='6xdc' size='340' side='right'caption='[[6xdc]], [[Resolution\|resolution]] 2.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6XDC OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6XDC FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6xdc]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/2019-ncov 2019-ncov]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6XDC OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6XDC FirstGlance]. <br>
-	</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=6xdc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xdc OCA], [http://pdbe.org/6xdc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6xdc RCSB], [http://www.ebi.ac.uk/pdbsum/6xdc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6xdc ProSAT]</span></td></tr>	+	</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">3a ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=2697049 2019-nCoV])</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=6xdc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xdc OCA], [http://pdbe.org/6xdc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6xdc RCSB], [http://www.ebi.ac.uk/pdbsum/6xdc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6xdc ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/AP3A_SARS2 AP3A_SARS2]] Forms homotetrameric potassium sensitive ion channels (viroporin) and may modulate virus release. Up-regulates expression of fibrinogen subunits FGA, FGB and FGG in host lung epithelial cells. Induces apoptosis in cell culture. Downregulates the type 1 interferon receptor by inducing serine phosphorylation within the IFN alpha-receptor subunit 1 (IFNAR1) degradation motif and increasing IFNAR1 ubiquitination.[UniProtKB:P59632]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	SARS-CoV-2 encodes three putative ion channels: E, 8a, and 3a. In related SARS-CoV-1, 3a is implicated in viral release, inflammasome activation, and cell death and its deletion reduces viral titer and morbidity in animal models, suggesting 3a-targeted therapeutics could treat SARS and COVID-19. However, the structural basis for the function of 3a is unknown. Here, we show that SARS-CoV-2 forms large conductance cation channels and present cryo-EM structures of dimeric and tetrameric SARS-CoV-2 3a in lipid nanodiscs. 3a adopts a novel fold and is captured in a closed or inactivated state. A narrow bifurcated exterior pore precludes conduction and leads to a large polar cavity open to the cytosol. 3a function is conserved in a common variant among circulating SARS-CoV-2 that alters the channel pore. We identify 3a-like proteins in Alpha- and Beta-coronaviruses that infect bats and humans, suggesting therapeutics targeting 3a could treat a range of coronaviral diseases.
		+
		+	Cryo-EM structure of the SARS-CoV-2 3a ion channel in lipid nanodiscs.,Kern DM, Sorum B, Hoel CM, Sridharan S, Remis JP, Toso DB, Brohawn SG bioRxiv. 2020 Jun 18. doi: 10.1101/2020.06.17.156554. PMID:32587976<ref>PMID:32587976</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6xdc" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: 2019-ncov]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Brohawn SG]]	+	[[Category: Brohawn, S G]]
-	[[Category: Hoel CM]]	+	[[Category: Hoel, C M]]
-	[[Category: Kern DM]]	+	[[Category: Kern, D M]]
		+	[[Category: Coronavirus]]
		+	[[Category: Ion channel]]
		+	[[Category: Sars-cov-2]]
		+	[[Category: Transport protein]]
		+	[[Category: Viroporin]]

OCA: Protected "6xdc" [edit=sysop:move=sysop]

2020-06-17T10:16:42Z

Protected "6xdc" [edit=sysop:move=sysop]

←Older revision

Revision as of 10:16, 17 June 2020

OCA: New page: ==Cryo-EM structure of SARS-CoV-2 ORF3a== == Structural highlights ==
Full cry...
2020-06-17T10:16:40Z

New page: ==Cryo-EM structure of SARS-CoV-2 ORF3a== <StructureSection load='6xdc' size='340' side='right'caption='6xdc' scene=''> == Structural highlights == <table><tr><td colspan='2'>Full cry...

New page

==Cryo-EM structure of SARS-CoV-2 ORF3a==
<StructureSection load='6xdc' size='340' side='right'caption='[[6xdc]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6XDC OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6XDC FirstGlance]. <br>
</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=6xdc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xdc OCA], [http://pdbe.org/6xdc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6xdc RCSB], [http://www.ebi.ac.uk/pdbsum/6xdc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6xdc ProSAT]</span></td></tr>
</table>
TOC
</StructureSection>
[[Category: Large Structures]]
[[Category: Brohawn SG]]
[[Category: Hoel CM]]
[[Category: Kern DM]]