8hqv

The complex structure of COPI cargo sorting module with HCoV-OC43 Spike KTSHxx sorting motif

spinqualitylabelsall models 8hqv, resolution 1.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8hqv is a 2 chain structure with sequence from Human coronavirus OC43 and Saccharomyces cerevisiae YJM789. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.398Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function COPB2_YEAST The coatomer is a cytosolic protein complex that binds to dilysine motifs and reversibly associates with Golgi non-clathrin-coated vesicles, which further mediate biosynthetic protein transport from the ER, via the Golgi up to the trans Golgi network. Coatomer complex is required for budding from Golgi membranes, and is essential for the retrograde Golgi-to-ER transport of dilysine-tagged proteins. Publication Abstract from PubMed Via an insufficient coat protein complex I (COPI) retrieval signal, the majority of SARS-CoV-2 spike (S) is resident in host early secretory organelles and a tiny amount is leaked out in cell surface. Only surface-exposed S can be recognized by B cell receptor (BCR) or anti-S therapeutic monoclonal antibodies (mAbs) that is the trigger step for B cell activation after S mRNA vaccination or infected cell clearance by S mAbs. Now, a drug strategy to promote S host surface exposure is absent. Here, we first combined structural and biochemical analysis to characterize S COPI sorting signals. A potent S COPI sorting inhibitor was then invented, evidently capable of promoting S surface exposure and facilitating infected cell clearance by S antibody-dependent cellular cytotoxicity (ADCC). Importantly, with the inhibitor as a probe, we revealed Omicron BA.1 S is less cell surface exposed than prototypes because of a constellation of S folding mutations, possibly corresponding to its ER chaperone association. Our findings not only suggest COPI is a druggable target against COVID-19, but also highlight SARS-CoV-2 evolution mechanism driven by S folding and trafficking mutations. SARS-CoV-2 spike host cell surface exposure promoted by a COPI sorting inhibitor.,Li Y, Yang M, Nan Y, Wang J, Wang S, Cui D, Guo J, He P, Dai W, Zhou S, Zhang Y, Ma W Acta Pharm Sin B. 2023 Apr 18;13(7):3043-53. doi: 10.1016/j.apsb.2023.04.007. PMID:37360012 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Coatomer 3D structures

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