Crystal structure of the receptor binding domain of the spike glycoprotein of human betacoronavirus HKU1.

Crystal structure of the receptor binding domain of the spike glycoprotein of human betacoronavirus HKU1.
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人β冠状病毒HKU1刺突糖蛋白受体结合域的晶体结构。

DOI:
10.1038/ncomms15216
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发表时间:
2017-05-23
影响因子:
16.6
通讯作者:
Cui S
Cui S
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Ou X;Guan H;Qin B;Mu Z;Wojdyla JA;Wang M;Dominguez SR;Qian Z;Cui S

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人类冠状病毒(CoV)HKU 1是一种引起急性呼吸道疾病的病原体,迄今为止对其生物学知之甚少。HKU 1病毒使用其S1亚基C末端结构域(CTD)而不是其他谱系A β-CoV的N末端结构域与其未知的人类受体结合。在这里,我们提出了HKU 1 CTD的晶体结构在1.9纳米分辨率。该结构由三个亚结构域组成:核心、插入和亚结构域-1(SD-1)。虽然HKU 1的核心和SD-1亚结构域的结构与其他β-CoV的结构高度相似,但插入亚结构域采用了一种新的折叠,这在HKU 1 S三聚体的冷冻EM结构中基本上是不可见的。我们确定了五个残基的插入子域中的中和抗体的结合是至关重要的和两个残基的受体结合必不可少的。我们的研究有助于更好地了解CoV S蛋白的进入、免疫和进化。人类冠状病毒HKU 1可在幼儿和免疫功能低下的患者中引起严重的呼吸道疾病。在这里,作者提出了病毒刺突糖蛋白S1亚基的C-末端结构域的结构,这是重要的宿主细胞受体结合。
Human coronavirus (CoV) HKU1 is a pathogen causing acute respiratory illnesses and so far little is known about its biology. HKU1 virus uses its S1 subunit C-terminal domain (CTD) and not the N-terminal domain like other lineage A β-CoVs to bind to its yet unknown human receptor. Here we present the crystal structure of HKU1 CTD at 1.9 Å resolution. The structure consists of three subdomains: core, insertion and subdomain-1 (SD-1). While the structure of the core and SD-1 subdomains of HKU1 are highly similar to those of other β-CoVs, the insertion subdomain adopts a novel fold, which is largely invisible in the cryo-EM structure of the HKU1 S trimer. We identify five residues in the insertion subdomain that are critical for binding of neutralizing antibodies and two residues essential for receptor binding. Our study contributes to a better understanding of entry, immunity and evolution of CoV S proteins. Human coronavirus HKU1 can cause severe respiratory diseases in young children and immunocompromised patients. Here, the authors present the structure of the C-terminal domain of the viral spike glycoprotein S1 subunit, which is important for host cell receptor binding.
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发表时间: 2009-06
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