CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; School of Medicine, Zhongda Hospital, Southeast University, Nanjing 210009, China.
Cell. 2022 Aug 4;185(16):2952-2960.e10. doi: 10.1016/j.cell.2022.06.023. Epub 2022 Jun 16.
The currently circulating Omicron sub-variants are the SARS-CoV-2 strains with the highest number of known mutations. Herein, we found that human angiotensin-converting enzyme 2 (hACE2) binding affinity to the receptor-binding domains (RBDs) of the four early Omicron sub-variants (BA.1, BA.1.1, BA.2, and BA.3) follows the order BA.1.1 > BA.2 > BA.3 ≈ BA.1. The complex structures of hACE2 with RBDs of BA.1.1, BA.2, and BA.3 reveal that the higher hACE2 binding affinity of BA.2 than BA.1 is related to the absence of the G496S mutation in BA.2. The R346K mutation in BA.1.1 majorly affects the interaction network in the BA.1.1 RBD/hACE2 interface through long-range alterations and contributes to the higher hACE2 affinity of the BA.1.1 RBD than the BA.1 RBD. These results reveal the structural basis for the distinct hACE2 binding patterns among BA.1.1, BA.2, and BA.3 RBDs.
目前流行的奥密克戎亚变体是已知突变数量最多的 SARS-CoV-2 株。在此，我们发现人类血管紧张素转换酶 2（hACE2）与四种早期奥密克戎亚变体（BA.1、BA.1.1、BA.2 和 BA.3）受体结合域（RBD）的结合亲和力顺序为 BA.1.1 > BA.2 > BA.3 ≈ BA.1。hACE2 与 BA.1.1、BA.2 和 BA.3 的 RBD 的复合物结构表明，BA.2 比 BA.1 具有更高的 hACE2 结合亲和力与 BA.2 中不存在 G496S 突变有关。BA.1.1 中的 R346K 突变主要通过远程改变影响 BA.1.1 RBD/hACE2 界面中的相互作用网络，并导致 BA.1.1 RBD 比 BA.1 RBD 具有更高的 hACE2 亲和力。这些结果揭示了 BA.1.1、BA.2 和 BA.3 RBD 之间 hACE2 结合模式的结构基础。
