Paul Scherrer Institut, Forschungsstrasse 111, 5232, Villigen, Switzerland.
Institut Laue-Langevin, 71 Avenue des Martyrs, BP 156, 38042, Grenoble, France.
Sci Rep. 2021 Jul 21;11(1):14867. doi: 10.1038/s41598-021-93996-x.
SARS-CoV-2 spike proteins are responsible for the membrane fusion event, which allows the virus to enter the host cell and cause infection. This process starts with the binding of the spike extramembrane domain to the angiotensin-converting enzyme 2 (ACE2), a membrane receptor highly abundant in the lungs. In this study, the extramembrane domain of SARS-CoV-2 Spike (sSpike) was injected on model membranes formed by supported lipid bilayers in presence and absence of the soluble part of receptor ACE2 (sACE2), and the structural features were studied at sub-nanometer level by neutron reflection. In all cases the presence of the protein produced a remarkable degradation of the lipid bilayer. Indeed, both for membranes from synthetic and natural lipids, a significant reduction of the surface coverage was observed. Quartz crystal microbalance measurements showed that lipid extraction starts immediately after sSpike protein injection. All measurements indicate that the presence of proteins induces the removal of membrane lipids, both in the presence and in the absence of ACE2, suggesting that sSpike molecules strongly associate with lipids, and strip them away from the bilayer, via a non-specific interaction. A cooperative effect of sACE2 and sSpike on lipid extraction was also observed.
SARS-CoV-2 刺突蛋白负责膜融合事件，该事件使病毒能够进入宿主细胞并引起感染。这个过程始于刺突跨膜域与血管紧张素转换酶 2（ACE2）的结合，ACE2 是一种在肺部高度丰富的膜受体。在这项研究中，SARS-CoV-2 刺突（sSpike）的跨膜域在存在和不存在可溶性受体 ACE2（sACE2）部分的情况下注入由支撑脂质双层形成的模型膜中，并通过中子反射在亚纳米水平研究了结构特征。在所有情况下，蛋白质的存在都会导致脂质双层明显降解。事实上，对于合成和天然脂质的膜，观察到表面覆盖率显著降低。石英晶体微天平测量表明，脂质提取在 sSpike 蛋白注入后立即开始。所有测量均表明，蛋白质的存在会导致膜脂质的去除，无论是在 ACE2 存在与否的情况下，这表明 sSpike 分子与脂质强烈结合，并通过非特异性相互作用将其从双层中剥离。还观察到 sACE2 和 sSpike 对脂质提取的协同作用。
