6xdc
From Proteopedia
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==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 [ | + | <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'>[ | + | </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: Severe acute respiratory syndrome coronavirus 2]] | ||
[[Category: Brohawn SG]] | [[Category: Brohawn SG]] | ||
[[Category: Hoel CM]] | [[Category: Hoel CM]] | ||
[[Category: Kern DM]] | [[Category: Kern DM]] | ||
Current revision
Cryo-EM structure of SARS-CoV-2 ORF3a
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