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研究揭示新冠病毒受体识别的结构基础
2020-03-31 15:42

美国明尼苏达大学李放课题组的一项最新研究解析了新冠病毒(SARS-CoV-2)受体识别的结构基础。2020年3月30日,《自然》在线发表了这一成果。

研究人员确定了与人类ACE2(hACE2)结合的SARS-CoV-2受体结合域(RBD)(经工程设计以促进结晶)的晶体结构。与SARS-CoV RBD相比,SARS-CoV-2 RBD中的hACE2结合脊具有更紧凑的构象。
 
SARS-CoV-2 RBD中的一些残基变化稳定了RBD/hACE2界面上的两个病毒结合热点。 SARS-CoV-2 RBD的这些结构特征增强了其hACE2结合亲和力。
 
此外,研究人员发现RaTG13,一种与SARS-CoV-2密切相关的蝙蝠冠状病毒,也使用hACE2作为其受体。hACE2识别中SARS-CoV-2、SARS-CoV和RaTG13之间的差异揭示了SARS-CoV-2潜在的人际传播。这项研究为针对SARS-CoV-2受体识别的干预策略提供了新见解。
 
附:英文原文

Title: Structural basis of receptor recognition by SARS-CoV-2

Author: Jian Shang, Gang Ye, Ke Shi, Yushun Wan, Chuming Luo, Hideki Aihara, Qibin Geng, Ashley Auerbach, Fang Li

Issue&Volume: 2020-03-30

Abstract: A novel SARS-like coronavirus (SARS-CoV-2) recently emerged and is rapidly spreading in humans1,2. A key to tackling this epidemic is to understand the virus’s receptor recognition mechanism, which regulates its infectivity, pathogenesis and host range. SARS-CoV-2 and SARS-CoV recognize the same receptor - human ACE2 (hACE2)3,4. Here we determined the crystal structure of the SARS-CoV-2 receptor-binding domain (RBD) (engineered to facilitate crystallization) in complex with hACE2. Compared with the SARS-CoV RBD, a hACE2-binding ridge in SARS-CoV-2 RBD takes a more compact conformation; moreover, several residue changes in SARS-CoV-2 RBD stabilize two virus-binding hotspots at the RBD/hACE2 interface. These structural features of SARS-CoV-2 RBD enhance its hACE2-binding affinity. Additionally, we show that RaTG13, a bat coronavirus closely related to SARS-CoV-2, also uses hACE2 as its receptor. The differences among SARS-CoV-2, SARS-CoV and RaTG13 in hACE2 recognition shed light on potential animal-to-human transmission of SARS-CoV-2. This study provides guidance for intervention strategies targeting receptor recognition by SARS-CoV-2.

DOI: 10.1038/s41586-020-2179-y

Source: https://www.nature.com/articles/s41586-020-2179-y

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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