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Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor

机译：结合ACE2受体的SARS-COV-2尖峰受体结合域的结构

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摘要

A new and highly pathogenic coronavirus (severe acute respiratory syndrome coronavirus-2, SARS-CoV-2) caused an outbreak in Wuhan city, Hubei province, China, starting from December 2019 that quickly spread nationwide and to other countries around the world(1-3). Here, to better understand the initial step of infection at an atomic level, we determined the crystal structure of the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 bound to the cell receptor ACE2. The overall ACE2-binding mode of the SARS-CoV-2 RBD is nearly identical to that of the SARS-CoV RBD, which also uses ACE2 as the cell receptor(4). Structural analysis identified residues in the SARS-CoV-2 RBD that are essential for ACE2 binding, the majority of which either are highly conserved or share similar side chain properties with those in the SARS-CoV RBD. Such similarity in structure and sequence strongly indicate convergent evolution between the SARS-CoV-2 and SARS-CoV RBDs for improved binding to ACE2, although SARS-CoV-2 does not cluster within SARS and SARS-related coronaviruses(1-3,5). The epitopes of two SARS-CoV antibodies that target the RBD are also analysed for binding to the SARS-CoV-2 RBD, providing insights into the future identification of cross-reactive antibodies.
机译：一种新的和高致病性冠状病毒（严重急性呼吸综合征Coronavirus-2，SARS-COV-2）在中国湖北省武汉市爆发了中国，从2019年12月开始，迅速将全国各地的全国各地传播到世界各国（1 -3）。这里，为了更好地了解在原子水平下感染的初始步骤，我们确定了与细胞受体Ace2结合的SARS-COV-2的尖峰蛋白的受体结合结构域（RBD）的晶体结构。 SARS-COV-2 RBD的总体ACE2结合模式几乎与SARS-COV RBD的结合模式几乎相同，其也使用ACE2作为细胞受体（4）。结构分析鉴定了SARS-COV-2 RBD中的残留物，这对于ACE2结合至关重要，其中大多数是高度保守的或与SARS-COV RBD中的那些具有相似的侧链性能。结构和序列中的这种相似性强烈地指示SARS-COV-2和SARS-COV RBD之间的会聚演化，以改善与ACE2的结合，尽管SARS-COV-2在SARS和SARS相关的冠状虫病毒（1-3,5中）。还分析了靶向RBD的两个SARS-COV抗体的表位用于与SARS-COV-2 RBD结合，为未来反应抗体的未来鉴定提供见解。

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  • 来源
    《Nature》 |2020年第7807期|215-220|共6页
  • 作者

    Lan Jun; Ge Jiwan; Yu Jinfang; Shan Sisi; Zhou Huan; Fan Shilong; Zhang Qi; Shi Xuanling; Wang Qisheng; Zhang Linqi; Wang Xinquan;

  • 作者单位

    Tsinghua Univ Beijing Adv Innovat Ctr Struct Biol Beijing Frontier Res Ctr Biol Struct Key Lab Prot Collaborat Innovat Ctr Biotherapy Minist Educ Sch Beijing Peoples R China;

    Tsinghua Univ Beijing Adv Innovat Ctr Struct Biol Beijing Frontier Res Ctr Biol Struct Key Lab Prot Collaborat Innovat Ctr Biotherapy Minist Educ Sch Beijing Peoples R China;

    Tsinghua Univ Beijing Adv Innovat Ctr Struct Biol Beijing Frontier Res Ctr Biol Struct Key Lab Prot Collaborat Innovat Ctr Biotherapy Minist Educ Sch Beijing Peoples R China;

    Tsinghua Univ Beijing Adv Innovat Ctr Struct Biol Ctr Global Hlth & Infect Dis Comprehens AIDS Res Ctr Sch Med Beijing Peoples R China;

    Chinese Acad Sci Shanghai Adv Res Inst Shanghai Synchrotron Radiat Facil Shanghai Peoples R China;

    Tsinghua Univ Beijing Adv Innovat Ctr Struct Biol Beijing Frontier Res Ctr Biol Struct Key Lab Prot Collaborat Innovat Ctr Biotherapy Minist Educ Sch Beijing Peoples R China;

    Tsinghua Univ Beijing Adv Innovat Ctr Struct Biol Ctr Global Hlth & Infect Dis Comprehens AIDS Res Ctr Sch Med Beijing Peoples R China;

    Tsinghua Univ Beijing Adv Innovat Ctr Struct Biol Ctr Global Hlth & Infect Dis Comprehens AIDS Res Ctr Sch Med Beijing Peoples R China;

    Chinese Acad Sci Shanghai Adv Res Inst Shanghai Synchrotron Radiat Facil Shanghai Peoples R China;

    Tsinghua Univ Beijing Adv Innovat Ctr Struct Biol Ctr Global Hlth & Infect Dis Comprehens AIDS Res Ctr Sch Med Beijing Peoples R China;

    Tsinghua Univ Beijing Adv Innovat Ctr Struct Biol Beijing Frontier Res Ctr Biol Struct Key Lab Prot Collaborat Innovat Ctr Biotherapy Minist Educ Sch Beijing Peoples R China;

  • 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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