7ye8

Crystal structure of SARS-CoV-2 refolded dimeric ORF9b

spinqualitylabelsall models 7ye8, resolution 3.01Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7ye8 is a 4 chain structure with sequence from Severe acute respiratory syndrome coronavirus 2. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.01Å Ligands: OCT Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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