8eny
From Proteopedia
Crystal structure of alpha-COPI-WD40 domain R13A mutant.
Structural highlights
FunctionCOPA_SCHPO 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 (By similarity). Publication Abstract from PubMedThe spike (S) protein of SARS-CoV-2 is delivered to the virion assembly site in the ER-Golgi Intermediate Compartment (ERGIC) from both the ER and cis-Golgi in infected cells. However, the relevance and modulatory mechanism of this bidirectional trafficking are unclear. Here, using structure-function analyses, we show that S incorporation into virus-like particles (VLP) and VLP fusogenicity are determined by coatomer-dependent S delivery from the cis-Golgi and restricted by S-coatomer dissociation. Although S mimicry of the host coatomer-binding dibasic motif ensures retrograde trafficking to the ERGIC, avoidance of the host-like C-terminal acidic residue is critical for S-coatomer dissociation and therefore incorporation into virions or export for cell-cell fusion. Because this C-terminal residue is the key determinant of SARS-CoV-2 assembly and fusogenicity, our work provides a framework for the export of S protein encoded in genetic vaccines for surface display and immune activation. A single C-terminal residue controls SARS-CoV-2 spike trafficking and incorporation into VLPs.,Dey D, Qing E, He Y, Chen Y, Jennings B, Cohn W, Singh S, Gakhar L, Schnicker NJ, Pierce BG, Whitelegge JP, Doray B, Orban J, Gallagher T, Hasan SS Nat Commun. 2023 Dec 15;14(1):8358. doi: 10.1038/s41467-023-44076-3. PMID:38102143[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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