Structural basis of receptor recognition by SARS-CoV-2
Structural basis of receptor recognition by SARS-CoV-2
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DOI：
10.1038/s41586-020-2179-y
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发表时间：
2020-03-30
期刊：
影响因子：
64.8
通讯作者：
Li, Fang
中科院分区：
文献类型：
--
作者：
Shang, Jian;Ye, Gang;Li, Fang
与SARS-CoV的受体结合域相比，SARS-CoV-2刺突与人类ACE2复合物的受体结合域的晶体结构揭示了增加其与ACE2结合亲和力的结构特征。最近出现了一种新型严重急性呼吸系统综合征（SARS）样冠状病毒（SARS- cov -2），并在人类中迅速传播，导致COVID-19（1,2）。应对此次大流行的关键是了解病毒的受体识别机制，该机制调节其传染性、发病机制和宿主范围。SARS-CoV-2和SARS-CoV在人类中识别相同的受体——血管紧张素转换酶2 (ACE2)（3,4）。在这里，我们确定了SARS-CoV-2刺突蛋白的受体结合域（RBD）与ACE2复合物的晶体结构（旨在促进结晶）。与SARS-CoV-2 RBD相比，SARS-CoV-2 RBD的ace2结合脊结构更紧凑；此外，SARS-CoV-2 RBD中的几个残基变化稳定了RBD- ace2界面上的两个病毒结合热点。SARS-CoV-2 RBD的这些结构特征增加了其与ace2结合的亲和力。此外，我们发现与SARS-CoV-2密切相关的蝙蝠冠状病毒RaTG13也使用人类ACE2作为其受体。SARS-CoV-2、SARS-CoV和RaTG13在ACE2识别上的差异为SARS-CoV-2可能的动物-人传播提供了线索。本研究为针对SARS-CoV-2受体识别的干预策略提供指导。
The crystal structure of the receptor-binding domain of the SARS-CoV-2 spike in complex with human ACE2, compared with the receptor-binding domain of SARS-CoV, sheds light on the structural features that increase its binding affinity to ACE2.A novel severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2) recently emerged and is rapidly spreading in humans, causing COVID-19(1,2). A key to tackling this pandemic is to understand the receptor recognition mechanism of the virus, which regulates its infectivity, pathogenesis and host range. SARS-CoV-2 and SARS-CoV recognize the same receptor-angiotensin-converting enzyme 2 (ACE2)-in humans(3,4). Here we determined the crystal structure of the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 (engineered to facilitate crystallization) in complex with ACE2. In comparison with the SARS-CoV RBD, an ACE2-binding ridge in SARS-CoV-2 RBD has a more compact conformation; moreover, several residue changes in the SARS-CoV-2 RBD stabilize two virus-binding hotspots at the RBD-ACE2 interface. These structural features of SARS-CoV-2 RBD increase its ACE2-binding affinity. Additionally, we show that RaTG13, a bat coronavirus that is closely related to SARS-CoV-2, also uses human ACE2 as its receptor. The differences among SARS-CoV-2, SARS-CoV and RaTG13 in ACE2 recognition shed light on the potential animal-to-human transmission of SARS-CoV-2. This study provides guidance for intervention strategies that target receptor recognition by SARS-CoV-2.