A Suitable Membrane Distance Regulated by the RBD_ACE2 Interaction is Critical for SARS‐CoV‐2 Spike‐Mediated Viral Invasion
Abstract: The receptor‐binding domain (RBD) of spike recognizing the receptor angiotensin‐converting enzyme 2 (ACE2) initiates membrane fusion between severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and cell membrane. Although the structure of the RBD_ACE2 complex has been well studied, its functional mechanism in membrane fusion is still not fully understood. Here, using an in vitro cell–vesicle content‐mixing assay, it is found that the cleavage at the S2’ site by thrombin (Thr) protease strongly accelerates membrane fusion, compared to that of cleavage at the S1/S2 site by PreScission (3C) protease. Moreover, mutations at the RBD_ACE2 interface resulted in a positive correlation between binding affinity and fusion probability. In both the cell–vesicle and cell–cell fusion assays, by crosslinking two membranes via the neutravidin (NTV) _biotin interaction or complementary DNA strands, it is found that spike drives membrane fusion in the absence of ACE2, and a suitable distance between two membranes is critical for spike‐mediated membrane fusion. Finally, unsuitable membrane crosslinkers significantly inhibited the fusion probability in the presence of ACE2. Taken together, the results suggest that the RBD_ACE2 complex may act as a crosslinker to bridge the viral and cell membranes at a suitable distance, which is critical, but also substitutable for spike‐mediated SARS‐CoV‐2 entry.
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Bibliographic citation
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A Suitable Membrane Distance Regulated by the RBD_ACE2 Interaction is Critical for SARS‐CoV‐2 Spike‐Mediated Viral Invasion ; day:17 ; month:08 ; year:2023 ; extent:15
Advanced science ; (17.08.2023) (gesamt 15)
- Creator
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Wu, Mengdan
Li, Wei
Lin, Sheng
Fan, Jiaqi
Cui, Lele
Xiang, Yijuan
Li, Kaiyu
Tang, Linwei
Duan, Yanping
Chen, Zimin
Yang, Fanli
Shui, Weiwei
Lu, Guangwen
Lai, Ying
- DOI
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10.1002/advs.202301478
- URN
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urn:nbn:de:101:1-2023081815071579391687
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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14.08.2025, 10:57 AM CEST
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Wu, Mengdan
- Li, Wei
- Lin, Sheng
- Fan, Jiaqi
- Cui, Lele
- Xiang, Yijuan
- Li, Kaiyu
- Tang, Linwei
- Duan, Yanping
- Chen, Zimin
- Yang, Fanli
- Shui, Weiwei
- Lu, Guangwen
- Lai, Ying
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