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====
==Cryo-EM structure of SARS-CoV-2 ORF3a==
<StructureSection load='7kjr' size='340' side='right'caption='[[7kjr]]' scene=''>
<StructureSection load='7kjr' size='340' side='right'caption='[[7kjr]], [[Resolution|resolution]] 2.08&Aring;' 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= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>
<table><tr><td colspan='2'>[[7kjr]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [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=7KJR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KJR 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=7kjr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kjr OCA], [https://pdbe.org/7kjr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kjr RCSB], [https://www.ebi.ac.uk/pdbsum/7kjr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kjr ProSAT]</span></td></tr>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PEE:1,2-DIOLEOYL-SN-GLYCERO-3-PHOSPHOETHANOLAMINE'>PEE</scene></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=7kjr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kjr OCA], [https://pdbe.org/7kjr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kjr RCSB], [https://www.ebi.ac.uk/pdbsum/7kjr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kjr 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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7kjr" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Z-disk]]
[[Category: Severe acute respiratory syndrome coronavirus 2]]
[[Category: Brohawn SG]]
[[Category: Hoel CM]]
[[Category: Kern DM]]
[[Category: Kotecha A]]
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