SARS-CoV-2 Spike 蛋白与 ACE2 的相互作用可诱导皮质肌动蛋白的调节,包括 ERM 蛋白的去磷酸化和皮质硬度的降低。

IF 4.3 3区 材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC ACS Applied Electronic Materials Pub Date : 2024-10-22 DOI:10.1007/s13577-024-01142-2
Thi Ly Do, Kouichi Tachibana, Norio Yamamoto, Kiyoshi Ando, Takaaki Isoda, Takanori Kihara
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引用次数: 0

摘要

细胞表面皮质肌动蛋白是病毒感染的调控靶标。我们的目的是研究严重急性呼吸系统综合征冠状病毒 2(SARS-CoV-2)感染对宿主细胞皮质硬度(皮质肌动蛋白结构的指标)的影响。SARS-CoV-2 Spike(S)蛋白的受体结合域(RBD)诱导表达 ACE2 的细胞皮质硬度降低。RBD 与 ACE2 的相互作用导致 Ezrin/Radixin/Moesin(ERM)蛋白失活。我们进一步研究了 SARS-CoV-2 Omicron 变体 BA.1 和 BA.5 的 RBD 的影响。这些 RBD 对皮质硬度的影响取决于它们对 ACE2 的亲和力。我们的研究首次证明了 SARS-CoV-2 S 蛋白与 ACE2 的相互作用会诱导机械生物学信号并减弱大脑皮层肌动蛋白。
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Interaction of SARS-CoV-2 Spike protein with ACE2 induces cortical actin modulation, including dephosphorylation of ERM proteins and reduction of cortical stiffness.

Cell surface cortical actin is a regulatory target for viral infection. We aimed to investigate the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on host cell cortical stiffness, an indicator of cortical actin structure. The receptor-binding domain (RBD) of SARS-CoV-2 Spike (S) protein induced a reduction in cortical stiffness in ACE2-expressing cells. The interaction of RBD with ACE2 caused the inactivation of Ezrin/Radixin/Moesin (ERM) proteins. We further investigated the effects of the RBD of SARS-CoV-2 Omicron variants, BA.1 and BA.5. These RBDs influenced cortical stiffness depending on their affinity for ACE2. Our study provides the first evidence that the interaction of the SARS-CoV-2 S protein with ACE2 induces mechanobiological signals and attenuates the cortical actin.

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