Structural basis for human coronavirus attachment to sialic acid receptors
Structural basis for human coronavirus attachment to sialic acid receptors
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DOI：
10.1038/s41594-019-0233-y
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发表时间：
2019-06-01
影响因子：
16.8
通讯作者：
Veesler, David
中科院分区：
文献类型：
--
作者：
Tortorici, M. Alejandra;Walls, Alexandra C.;Veesler, David
冠状病毒引起人类呼吸道感染，并在全球范围内爆发致命的肺炎。感染是由跨膜刺突（S）糖蛋白引发的，它与宿主受体结合并融合病毒和细胞膜。为了了解冠状病毒附着于寡糖受体的分子基础，我们确定了冠状病毒OC 43 S糖蛋白三聚体的分离和与9-O-乙酰化唾液酸的复合物的冷冻电镜结构。我们表明，配体结合与快速动力学的表面暴露的凹槽，并在确定的网站的相互作用是必不可少的S-介导的病毒进入宿主细胞，但游离单糖不触发融合构象变化。受体相互作用位点在所有与9-O-乙酰基-唾液酸聚糖结合的冠状病毒S糖蛋白中是保守的，其结构类似于冠状病毒血凝素酯酶和流感病毒C/D血凝素-酯酶融合糖蛋白的配体结合口袋。我们的研究结果表明，这些病毒进化出类似的策略，在靶细胞表面接合唾液酸聚糖。
Coronaviruses cause respiratory tract infections in humans and outbreaks of deadly pneumonia worldwide. Infections are initiated by the transmembrane spike (S) glycoprotein, which binds to host receptors and fuses the viral and cellular membranes. To understand the molecular basis of coronavirus attachment to oligosaccharide receptors, we determined cryo-EM structures of coronavirus OC43 S glycoprotein trimer in isolation and in complex with a 9-O-acetylated sialic acid. We show that the ligand binds with fast kinetics to a surface-exposed groove and that interactions at the identified site are essential for S-mediated viral entry into host cells, but free monosaccharide does not trigger fusogenic conformational changes. The receptor-interacting site is conserved in all coronavirus S glycoproteins that engage 9-O-acetyl-sialogycans, with an architecture similar to those of the ligand-binding pockets of coronavirus hemagglutinin esterases and influenza virus C/D hemagglutinin-esterase fusion glycoproteins. Our results demonstrate these viruses evolved similar strategies to engage sialoglycans at the surface of target cells.