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与ACE2受体结合的SARS-CoV-2尖端受体结合域的结构

Jun Lan¹, Jiwan Ge¹, Jinfang Yu¹

¹The Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center for Biological Structure, Collaborative Innovation Center for Biotherapy, School of Life Sciences, Tsinghua University, Beijing, China.

|April 1, 2020

概括

研究人员确定了与ACE2结合的SARS-CoV-2尖端蛋白的受体结合域 (RBD) 的晶体结构. 这揭示了关键的残留物,并表明与ACE2受体结合的趋同演变.

科学领域:

病毒学
结构生物学
生物化学

背景情况:

2019年底出现的SARS-CoV-2导致全球大流行.
在分子层面了解最初的感染机制至关重要.
尖端蛋白的受体结合域 (RBD) 通过ACE2介导细胞进入.

研究的目的:

阐明SARS-CoV-2 RBD和ACE2之间的原子级相互作用.
识别SARS-CoV-2 RBD中的关键残留物,这些残留物对于ACE2结合至关重要.
为了比较SARS-CoV-2和SARS-CoV RBD的结合机制.

主要方法:

使用X射线结晶学来确定SARS-CoV-2 RBD-ACE2复合体的结构.
进行结构分析以确定关键的氨基酸残留物.
与SARS-CoV RBD进行了结构和序列数据的比较.

主要成果:

确定了与ACE2结合的SARS-CoV-2 RBD的晶体结构.
SARS-CoV-2 RBD 与 ACE2 的结合方式与 SARS-CoV RBD 的结合方式非常相似.
在SARS-CoV-2 RBD中发现了ACE2结合的关键残留物,许多残留物保留或与SARS-CoV RBD类似.

结论:

结构和序列的相似性表明SARS-CoV-2和SARS-CoV RBD之间的融合进化可以改善ACE2结合.
这些发现提供了SARS-CoV-2进入分子基础的见解.
对抗体表位的分析为产生交叉反应性抗体提供了潜力.

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