Cryo-EM analysis of the post-fusion structure of the SARS-CoV spike glycoprotein
Cryo-EM analysis of the post-fusion structure of the SARS-CoV spike glycoprotein
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SARS-CoV 刺突糖蛋白融合后结构的冷冻电镜分析
DOI：
10.1038/s41467-020-17371-6
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发表时间：
2020-07-17
影响因子：
16.6
通讯作者：
Zhang, Xinzheng
中科院分区：
文献类型：
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作者：
Fan, Xiaoyi;Cao, Duanfang;Zhang, Xinzheng
由严重急性呼吸综合征冠状病毒（SARS-CoV）、中东呼吸综合征冠状病毒（MERS-CoV）和SARS-CoV-2引起的全球突发事件严重危害人类健康。刺突(S)糖蛋白是关键抗原，其保守的S2亚基通过介导宿主-病毒膜融合参与病毒进入。然而，这些高致病性人感染冠状病毒融合后S2的结构信息仍然缺乏。我们使用单粒子冷冻电子显微镜发现，融合后的SARS-CoV S2形成了HR1-HR2的进一步旋转的六螺旋束和HR2基序上游的紧密结合的连接区域。SARS-CoV融合前和融合后的糖蛋白结构存在显著差异，与小鼠肝炎病毒（MHV）和其他I类病毒融合蛋白的结构相似。这种结构为开发针对多种sars样冠状病毒的疫苗和疗法提供了潜在的目标。
Global emergencies caused by the severe acute respiratory syndrome coronavirus (SARS-CoV), Middle-East respiratory syndrome coronavirus (MERS-CoV) and SARS-CoV-2 significantly endanger human health. The spike (S) glycoprotein is the key antigen and its conserved S2 subunit contributes to viral entry by mediating host-viral membrane fusion. However, structural information of the post-fusion S2 from these highly pathogenic human-infecting coronaviruses is still lacking. We used single-particle cryo-electron microscopy to show that the post-fusion SARS-CoV S2 forms a further rotated HR1-HR2 six-helix bundle and a tightly bound linker region upstream of the HR2 motif. The structures of pre- and post-fusion SARS-CoV S glycoprotein dramatically differ, resembling that of the Mouse hepatitis virus (MHV) and other class I viral fusion proteins. This structure suggests potential targets for the development of vaccines and therapies against a wide range of SARS-like coronaviruses.