8ENS

Crystal structure of beta'-COPI-WD40 domain in complex with SARS-CoV-2 spike tail hepta-peptide

8ENS の概要

• エントリーDOI: 10.2210/pdb8ens/pdb
• 分子名称: Coatomer subunit beta', spike tail hepta-peptide (3 entities in total)
• 機能のキーワード: copi, protein trafficking, sars-cov-2 spike, dibasic motif, protein transport
• 由来する生物種: Saccharomyces cerevisiae (baker's yeast); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 35199.69

構造登録者

Dey, D.,Hasan, S.S. (登録日: 2022-09-30, 公開日: 2024-01-31)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.45 Å)