School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, China.
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
Nat Commun. 2017 Apr 10;8:15092. doi: 10.1038/ncomms15092.
The envelope spike (S) proteins of MERS-CoV and SARS-CoV determine the virus host tropism and entry into host cells, and constitute a promising target for the development of prophylactics and therapeutics. Here, we present high-resolution structures of the trimeric MERS-CoV and SARS-CoV S proteins in its pre-fusion conformation by single particle cryo-electron microscopy. The overall structures resemble that from other coronaviruses including HKU1, MHV and NL63 reported recently, with the exception of the receptor binding domain (RBD). We captured two states of the RBD with receptor binding region either buried (lying state) or exposed (standing state), demonstrating an inherently flexible RBD readily recognized by the receptor. Further sequence conservation analysis of six human-infecting coronaviruses revealed that the fusion peptide, HR1 region and the central helix are potential targets for eliciting broadly neutralizing antibodies.
包膜刺突（S）蛋白决定了 MERS-CoV 和 SARS-CoV 的病毒宿主趋向性和进入宿主细胞的能力，是开发预防和治疗药物的有前途的靶点。在这里，我们通过单颗粒冷冻电镜展示了三聚体 MERS-CoV 和 SARS-CoV S 蛋白在其预融合构象下的高分辨率结构。这些结构与其他冠状病毒（包括最近报道的 HKU1、MHV 和 NL63）的结构相似，除了受体结合域（RBD）。我们捕捉到了两种 RBD 状态，受体结合区域要么被掩埋（躺着状态），要么暴露（站立状态），这表明 RBD 具有固有灵活性，很容易被受体识别。对六种感染人类的冠状病毒的进一步序列保守性分析表明，融合肽、HR1 区和中心螺旋是引发广泛中和抗体的潜在靶点。
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