Glycan shield and epitope masking of a coronavirus spike protein observed by cryo-electron microscopy.
Glycan shield and epitope masking of a coronavirus spike protein observed by cryo-electron microscopy.
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DOI：
10.1038/nsmb.3293
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发表时间：
2016-10
影响因子：
16.8
通讯作者：
Veesler D
中科院分区：
文献类型：
--
作者：
Walls AC;Tortorici MA;Frenz B;Snijder J;Li W;Rey FA;DiMaio F;Bosch BJ;Veesler D
对冠状病毒hCoV-NL63的尖峰糖蛋白三聚体的冷冻-EM和质谱分析显示，覆盖在蛋白质表面的广泛的糖蛋白保护层，包括针对几种冠状病毒的中和抗体靶向的表位。本文的在线版本(doi：10.1038/nsmb.3293)包含补充材料，授权用户可以使用。重大冠状病毒大流行的威胁促使制定与这些病原体作斗争的战略。人类冠状病毒NL63(HCoVNL63)是一种α冠状病毒，可导致严重的下呼吸道感染，需要住院治疗。我们在这里报道了HCoV-NL63冠状病毒刺突糖蛋白三聚体的3.4-分辨率冷冻-EM重建，该三聚体介导进入宿主细胞，是感染期间中和抗体的主要目标。MAP解决了阻碍蛋白质表面的广泛的葡聚糖屏障，并与质谱学相结合，提供了一个结构框架来了解抗体的可及性。该结构揭示了融合机制的完整架构，包括触发环和C-末端结构域，它们有助于将三聚体锚定在病毒膜上。我们的数据进一步表明，HCoV-NL63和其他冠状病毒使用基于糖链表位掩蔽和激活构象变化的分子诡计来逃避受感染宿主的免疫系统。本文的在线版本(doi：10.1038/nsmb.3293)包含补充材料，授权用户可以使用。
Cryo-EM and mass spectrometry analyses of the spike glycoprotein trimer from coronavirus HcoV-NL63 reveal an extensive glycan shield that covers the protein surface, including an epitope targeted by neutralizing antibodies against several coronaviruses. The online version of this article (doi:10.1038/nsmb.3293) contains supplementary material, which is available to authorized users. The threat of a major coronavirus pandemic urges the development of strategies to combat these pathogens. Human coronavirus NL63 (HCoV-NL63) is an α-coronavirus that can cause severe lower-respiratory-tract infections requiring hospitalization. We report here the 3.4-Å-resolution cryo-EM reconstruction of the HCoV-NL63 coronavirus spike glycoprotein trimer, which mediates entry into host cells and is the main target of neutralizing antibodies during infection. The map resolves the extensive glycan shield obstructing the protein surface and, in combination with mass spectrometry, provides a structural framework to understand the accessibility to antibodies. The structure reveals the complete architecture of the fusion machinery including the triggering loop and the C-terminal domains, which contribute to anchoring the trimer to the viral membrane. Our data further suggest that HCoV-NL63 and other coronaviruses use molecular trickery, based on epitope masking with glycans and activating conformational changes, to evade the immune system of infected hosts. The online version of this article (doi:10.1038/nsmb.3293) contains supplementary material, which is available to authorized users.
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电子计数和束诱导运动校正可实现近原子分辨率的单粒子冷冻电镜。
影响因子：
48
作者：
Li, Xueming;Mooney, Paul;Zheng, Shawn;Booth, Christopher R.;Braunfeld, Michael B.;Gubbens, Sander;Agard, David A.;Cheng, Yifan
通讯作者：
Cheng, Yifan
DOI：
10.1074/jbc.m603275200
发表时间：
2006-11-10
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Hwang WC;Lin Y;Santelli E;Sui J;Jaroszewski L;Stec B;Farzan M;Marasco WA;Liddington RC
通讯作者：
Liddington RC
DOI：
10.1126/science.1234914
发表时间：
2013-05-31
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
McLellan JS;Chen M;Leung S;Graepel KW;Du X;Yang Y;Zhou T;Baxa U;Yasuda E;Beaumont T;Kumar A;Modjarrad K;Zheng Z;Zhao M;Xia N;Kwong PD;Graham BS
通讯作者：
Graham BS
DOI：
10.1073/pnas.1407087111
发表时间：
2014-10-21
影响因子：
11.1
作者：
Millet, Jean Kaoru;Whittaker, Gary R.
通讯作者：
Whittaker, Gary R.
影响因子：
11.8
作者：
Chiu, SS;Chan, KH;Peiris, JSM
通讯作者：
Peiris, JSM