Lipid bilayer degradation induced by SARS-CoV-2 spike protein as revealed by neutron reflectometry.
Lipid bilayer degradation induced by SARS-CoV-2 spike protein as revealed by neutron reflectometry.
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DOI：
10.1038/s41598-021-93996-x
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发表时间：
2021-07-21
影响因子：
4.6
通讯作者：
Fragneto G
中科院分区：
文献类型：
--
作者：
Luchini A;Micciulla S;Corucci G;Batchu KC;Santamaria A;Laux V;Darwish T;Russell RA;Thepaut M;Bally I;Fieschi F;Fragneto G
SARS-CoV-2刺突蛋白负责膜融合事件，该事件允许病毒进入宿主细胞并引起感染。这个过程开始于刺突膜外结构域与血管紧张素转换酶2（ACE 2）的结合，ACE 2是一种在肺中高度丰富的膜受体。在这项研究中，膜外结构域的SARS-CoV-2刺（sSpike）注射到支持的脂质双层形成的模型膜上，在存在和不存在的可溶性部分的受体ACE 2（sACE 2），并在亚纳米水平上的结构特征进行了研究，中子反射。在所有情况下，蛋白质的存在下产生了显着的降解的脂质双层。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。石英晶体微量天平测量显示，在sSpike蛋白注射后立即开始脂质提取。所有的测量结果表明，蛋白质的存在诱导膜脂质的去除，无论是在存在和不存在的ACE 2，这表明sSpike分子强烈地与脂质，并剥离它们远离双层，通过非特异性相互作用。还观察到sACE 2和sSpike对脂质提取的协同作用。
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.