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人类ACE2与目前流传的Omicron SARS-CoV-2亚型BA.2和BA.1.1的结构基础
Linjie Li1, Hanyi Liao1, Yumin Meng1
1CAS 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.
SARS-CoV-2 的 Omicron 亚型表现出许多突变. 由于其受体结合域 (RBD) 的特定突变,BA.1.1和BA.2的结合亲和力比BA.1和BA.3更高.
科学领域:
- 病毒学
- 结构生物学
- 生物化学
背景情况:
- SARS-CoV-2 的 Omicron 亚型具有较高的突变负载.
- 了解病毒变体与宿主细胞受体之间的相互作用对于评估感染性至关重要.
研究的目的:
- 调查早期Omicron亚型 (BA.1,BA.1.1,BA.2,BA.3) 与人类血管素转化酶2 (hACE2) 的结合亲和力.
- 阐明这些SARS-CoV-2变体之间的hACE2结合关系差异的结构基础.
主要方法:
- 对BA.1,BA.1.1,BA.2和BA.3的受体结合域 (RBDs) 的 hACE2结合 afinity 的比较分析
- 用BA.1.1,BA.2和BA.3中的RBD来确定HACE2的复杂结构.
主要成果:
- 确定了HACE2结合亲和度的顺序为BA.1.1>BA.2>BA.3 ≈BA.1.
- 与BA.1相比,BA.2的结合亲和力增加归因于G496S突变的缺失.
- 在BA.1.1中R346K突变显著影响RBD/hACE2接口,增强结合亲和力.
结论:
- 结构洞察力揭示了Omicron亚型BA.1.1,BA.2和BA.3的独特的HACE2结合模式.
- 在RBD中发生的特定突变决定了SARS-CoV-2变种的结合特性和潜在感染性.
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