Conformational reorganization of the SARS coronavirus spike following receptor binding: implications for membrane fusion.

Conformational reorganization of the SARS coronavirus spike following receptor binding: implications for membrane fusion.
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受体结合后SARS冠状病毒尖峰的构象重组:对膜融合的影响。

DOI:
10.1371/journal.pone.0001082
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发表时间:
2007-10-24
期刊:
影响因子:
3.7
通讯作者:
Booth TF
Booth TF
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Beniac DR;deVarennes SL;Andonov A;He R;Booth TF

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SARS 冠状病毒 (SARS-CoV) 刺突是已知最大的病毒刺突分子,与所有 1 类病毒融合蛋白具有相似的功能。先前的膜融合蛋白结构研究主要使用静态分子片段的晶体学,分离其跨膜结构域。在这项研究中,我们生产了纯化的、经过辐照的 SARS-CoV 病毒粒子,该病毒粒子保留了其形态,并且在细胞培养物中具有融合性。我们使用冷冻电子显微镜和图像处理来研究完整病毒颗粒与病毒受体血管紧张素转换酶 2 (ACE2) 结合时整个刺突发生的构象变化。我们已经证明,ACE2 结合会导致结构变化,这似乎是病毒膜融合的第一步,并且精确地将受体结合和融合核心结构域定位在整个刺突内。此外,我们的结果表明受体结合和随后的膜融合是不同的步骤,并且每个刺突最多可以结合三个 ACE2 分子。 SARS-CoV 刺突提供了一个理想的模型系统,可利用冷冻电子显微镜和单颗粒图像分析来研究天然状态下的受体结合和膜融合。
The SARS coronavirus (SARS-CoV) spike is the largest known viral spike molecule, and shares a similar function with all class 1 viral fusion proteins. Previous structural studies of membrane fusion proteins have largely used crystallography of static molecular fragments, in isolation of their transmembrane domains. In this study we have produced purified, irradiated SARS-CoV virions that retain their morphology, and are fusogenic in cell culture. We used cryo-electron microscopy and image processing to investigate conformational changes that occur in the entire spike of intact virions when they bind to the viral receptor, angiotensin-converting enzyme 2 (ACE2). We have shown that ACE2 binding results in structural changes that appear to be the initial step in viral membrane fusion, and precisely localized the receptor-binding and fusion core domains within the entire spike. Furthermore, our results show that receptor binding and subsequent membrane fusion are distinct steps, and that each spike can bind up to three ACE2 molecules. The SARS-CoV spike provides an ideal model system to study receptor binding and membrane fusion in the native state, employing cryo-electron microscopy and single-particle image analysis.
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DOI: 10.1083/jcb.139.6.1455
发表时间: 1997-12-15
期刊: The Journal of cell biology
影响因子: --
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期刊: EMBO JOURNAL
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