|
|
| 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]]
| |
