PDF(Pubmed)
Abstract：
Conformational dynamics of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein (S) mediate exposure of the binding site for the cellular receptor, angiotensin-converting enzyme 2 (ACE2). The N-terminal domain (NTD) of S binds terminal sialic acid (SA) moieties on the cell surface, but the functional role of this interaction in virus entry is unknown. Here, we report that NTD-SA interaction enhances both S-mediated virus attachment and ACE2 binding. Through single-molecule Förster resonance energy transfer imaging of individual S trimers, we demonstrate that SA binding to the NTD allosterically shifts the S conformational equilibrium, favoring enhanced exposure of the ACE2-binding site. Antibodies that target the NTD block SA binding, which contributes to their mechanism of neutralization. These findings inform on mechanisms of S activation at the cell surface.
摘要：
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）刺突糖蛋白（S）的构象动力学介导细胞受体结合位点的暴露，血管紧张素转换酶2（ACE2）。S的N末端结构域（NTD）结合细胞表面上的末端唾液酸（SA）部分，但是这种相互作用在病毒进入中的功能作用是未知的。这里,我们报道NTD-SA相互作用增强了S介导的病毒附着和ACE2结合.通过单个S三聚体的单分子Förster共振能量转移成像，我们证明了SA与NTD的结合变构地改变了S构象平衡，有利于增强ACE2结合位点的暴露。靶向NTD的抗体阻断SA结合，这有助于它们的中和机制。这些发现揭示了细胞表面S活化的机制。
