8ENX

Crystal structure of beta'-COPI-WD40 domain Y33A mutant in complex with SARS-CoV-2 clientized spike tail heptapeptide.

Summary for 8ENX

• Entry DOI: 10.2210/pdb8enx/pdb
• Descriptor: Coatomer subunit beta', Clientized spike tail heptapeptide (3 entities in total)
• Functional Keywords: copi, protein trafficking, sars-cov-2 spike, dibasic motif, protein transport
• Biological source: Saccharomyces cerevisiae (baker's yeast); More
• Total number of polymer chains: 3
• Total formula weight: 69424.24

Authors

Dey, D.,Hasan, S.S. (deposition date: 2022-09-30, release date: 2024-01-31)

Primary citation

Dey, D.,Qing, E.,He, Y.,Chen, Y.,Jennings, B.,Cohn, W.,Singh, S.,Gakhar, L.,Schnicker, N.J.,Pierce, B.G.,Whitelegge, J.P.,Doray, B.,Orban, J.,Gallagher, T.,Hasan, S.S.
A single C-terminal residue controls SARS-CoV-2 spike trafficking and incorporation into VLPs.
Nat Commun, 14:8358-8358, 2023

PubMed Abstract: The 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.

PubMed: 38102143
DOI: 10.1038/s41467-023-44076-3

Experimental method

X-RAY DIFFRACTION (1.8 Å)