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Structural basis of receptor recognition by SARS-CoV-2

机译：SARS-COV-2受体识别的结构基础

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摘要

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.
机译：最近出现了一种新型的严重急性呼吸综合征（SARS） - 蓖麻病毒（SARS-COV-2）并在人体中迅速蔓延，导致Covid-19（1,2）。解决这种大流行的关键是了解病毒的受体识别机制，该机制调节其感染性，发病机制和宿主范围。 SARS-COV-2和SARS-COV识别相同的受体 - 血管紧张素转换酶2（ACE2）-IN人（3,4）。在这里，我们确定了SARS-COV-2的尖峰蛋白（工程化以促进结晶）的受体结合结构域（RBD）的晶体结构，与ACE2复合物。与SARS-COV RBD相比，SARS-COV-2 RBD中的ACE2结合脊具有更紧凑的构象;此外，SARS-COV-2 RBD的几个残留物变化稳定了RBD-ACE2接口的两种病毒结合热点。 SARS-COV-2 RBD的这些结构特征增加了其ACE2结合亲和力。此外，我们表明RATG13是与SARS-COV-2密切相关的蝙蝠冠状病毒，也使用人ACE2作为其受体。 SARS-COV-2，SARS-COV和RATG13中的差异在ACE2识别揭示光线上SARS-COV-2的潜在动物对人体传播。本研究为SARS-COV-2定位受体识别的干预策略提供指导。

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  • 来源
    《Nature》 |2020年第7807期|221-224|共4页
  • 作者

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

  • 作者单位

    Univ Minnesota Dept Vet & Biomed Sci St Paul MN 55108 USA;

    Univ Minnesota Dept Vet & Biomed Sci St Paul MN 55108 USA;

    Univ Minnesota Dept Biochem Mol Biol & Biophys Minneapolis MN USA;

    Univ Minnesota Dept Vet & Biomed Sci St Paul MN 55108 USA;

    Univ Minnesota Dept Vet & Biomed Sci St Paul MN 55108 USA;

    Univ Minnesota Dept Biochem Mol Biol & Biophys Minneapolis MN USA;

    Univ Minnesota Dept Vet & Biomed Sci St Paul MN 55108 USA;

    Univ Minnesota Dept Vet & Biomed Sci St Paul MN 55108 USA;

    Univ Minnesota Dept Vet & Biomed Sci St Paul MN 55108 USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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  • 正文语种 eng
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