Cryo-EM structure of the SARS-CoV-2 Omicron spike.

Cryo-EM structure of the SARS-CoV-2 Omicron spike.
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DOI:
10.1016/j.celrep.2022.110428
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发表时间:
2022-03-01
期刊:
影响因子:
8.8
通讯作者:
Shapiro L
Shapiro L
中科院分区:
生物学1区
文献类型:
--
作者:
Cerutti G;Guo Y;Liu L;Liu L;Zhang Z;Luo Y;Huang Y;Wang HH;Ho DD;Sheng Z;Shapiro L

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最近报道的严重急性呼吸综合征冠状病毒-2 (SARS-CoV-2) 的 B.1.1.529 Omicron 变种与武汉毒株相比,在刺突蛋白中包含 34 个突变,其中包括受体结合域 (RBD) 中的 15 个突变。功能研究表明 Omicron 基本上避开了许多 SARS-CoV-2 中和抗体的活性。在这里,我们报告了 Omicron 刺突蛋白胞外域的 3.1 Å 分辨率冷冻电子显微镜 (cryo-EM) 结构。该结构描绘了仅处于 1-RBD-up 构象的尖峰,具有高 RBD 迁移率。许多突变会导致抗体结合表面的空间冲突和/或相互作用的改变,而其他突变则介导局部区域的刺突结构的变化以干扰抗体识别。总体而言,Omicron 刺突的结构揭示了突变如何改变其构象,并解释了其逃避中和抗体的非凡能力。切鲁蒂等人。报道了无配体形式的 SARS-CoV-2 Omicron 刺突的冷冻电镜结构。该结构阐明了突变对刺突整体和局部构象的影响,并解释了对 Omicron 变体的抗体抗性。
The recently reported B.1.1.529 Omicron variant of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) includes 34 mutations in the spike protein relative to the Wuhan strain, including 15 mutations in the receptor-binding domain (RBD). Functional studies have shown Omicron to substantially escape the activity of many SARS-CoV-2-neutralizing antibodies. Here, we report a 3.1 Å-resolution cryoelectron microscopy (cryo-EM) structure of the Omicron spike protein ectodomain. The structure depicts a spike that is exclusively in the 1-RBD-up conformation with high mobility of RBD. Many mutations cause steric clashes and/or altered interactions at antibody-binding surfaces, whereas others mediate changes of the spike structure in local regions to interfere with antibody recognition. Overall, the structure of the Omicron spike reveals how mutations alter its conformation and explains its extraordinary ability to evade neutralizing antibodies. Cerutti et al. report the cryo-EM structure of the SARS-CoV-2 Omicron spike in its ligand-free form. The structure elucidates the effect of the mutations on the global and local conformation of spike and explains the antibody resistance to the Omicron variant.
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