View source for 7ye8


==Crystal structure of SARS-CoV-2 refolded dimeric ORF9b==
<StructureSection load='7ye8' size='340' side='right'caption='[[7ye8]], [[Resolution|resolution]] 3.01&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7ye8]] is a 4 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=7YE8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7YE8 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.01&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=OCT:N-OCTANE'>OCT</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=7ye8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ye8 OCA], [https://pdbe.org/7ye8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ye8 RCSB], [https://www.ebi.ac.uk/pdbsum/7ye8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ye8 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ORF9B_SARS2 ORF9B_SARS2] Plays a role in inhibiting the host innate immune response by targeting the mitochondrial-associated innate immune response. Acts by binding to host TOMM70, inhibiting its binding to HSP90AB1 thereby disrupting the interferon activation pathway.<ref>PMID:32728199</ref> <ref>PMID:34502139</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The constant emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants indicates the evolution and adaptation of the virus. Enhanced innate immune evasion through increased expression of viral antagonist proteins, including ORF9b, contributes to the improved transmission of the Alpha variant; hence, more attention should be paid to these viral proteins. ORF9b is an accessory protein that suppresses innate immunity via a monomer conformation by binding to Tom70. Here, we solved the dimeric structure of SARS-CoV-2 ORF9b with a long hydrophobic tunnel containing a lipid molecule that is crucial for the dimeric conformation and determined the specific lipid ligands as monoglycerides by conducting a liquid chromatography with tandem mass spectrometry analysis, suggesting an important role in the viral life cycle. Notably, a long intertwined loop accessible for host factor binding was observed in the structure. Eight phosphorylated residues in ORF9b were identified, and residues S50 and S53 were found to contribute to the stabilization of dimeric ORF9b. Additionally, we proposed a model of multifunctional ORF9b with a distinct conformation, suggesting that ORF9b is a fold-switching protein, while both lipids and phosphorylation contribute to the switching. Specifically, the ORF9b monomer interacts with Tom70 to suppress the innate immune response, whereas the ORF9b dimer binds to the membrane involving mature virion assembly. Our results provide a better understanding of the multiple functions of ORF9b.

Structural characterization of SARS-CoV-2 dimeric ORF9b reveals potential fold-switching trigger mechanism.,Jin X, Sun X, Chai Y, Bai Y, Li Y, Hao T, Qi J, Song H, Wong CCL, Gao GF Sci China Life Sci. 2022 Sep 29. pii: 10.1007/s11427-022-2168-8. doi:, 10.1007/s11427-022-2168-8. PMID:36184694<ref>PMID:36184694</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7ye8" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Severe acute respiratory syndrome coronavirus 2]]
[[Category: Chai Y]]
[[Category: Gao GF]]
[[Category: Jin X]]
[[Category: Qi J]]
[[Category: Song H]]