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 cells1-3. However, the relevance and modulatory mechanism of this bidirectional trafficking are unclear. Here, using structure-function analyses, we show that S incorporation into virions and viral 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.

中文翻译：

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单个 C 端残基控制 SARS-CoV-2 尖峰运输和病毒粒子组装

SARS-CoV-2 的刺突 (S) 蛋白从受感染细胞中的内质网和顺式高尔基体输送到内质网高尔基体中间室 (ERGIC) 的病毒粒子组装位点 1-3。然而，这种双向贩运的相关性和调节机制尚不清楚。在这里，我们使用结构-功能分析表明，S 掺入病毒体和病毒融合性由顺式高尔基体依赖性 S 递送决定，并受 S-coatomer 解离的限制。尽管 S 对宿主辅酶结合二元基序的模拟确保逆行运输到 ERGIC，但避免宿主样 C 末端酸性残基对于 S 辅酶解离以及因此掺入病毒粒子或输出细胞融合至关重要。因为这个 C 端残基是 SARS-CoV-2 组装和融合的关键决定因素，