Biomechanical Characterization of SARS-CoV-2 Spike RBD and Human ACE2 Protein-Protein Interaction
| Autor: | X. Frank Zhang, Wenpeng Cao, Lanying Du, Wonpil Im, Wanbo Tai, Chuqiao Dong, Seonghan Kim, Decheng Hou |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Glycan
Coronavirus disease 2019 (COVID-19) Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viruses Protein domain Biophysics Plasma protein binding Models Biological Virus Article Protein–protein interaction 03 medical and health sciences Molecular dynamics 0302 clinical medicine Protein Domains Polysaccharides Humans Computer Simulation Receptor skin and connective tissue diseases 030304 developmental biology 0303 health sciences biology Chemistry HEK 293 cells fungi Force spectroscopy virus diseases Single Molecule Imaging respiratory tract diseases Biomechanical Phenomena body regions HEK293 Cells Spike Glycoprotein Coronavirus biology.protein Angiotensin-Converting Enzyme 2 030217 neurology & neurosurgery hormones hormone substitutes and hormone antagonists Protein Binding |
| Zdroj: | bioRxiv Biophysical Journal |
| Popis: | The current COVID-19 pandemic has led to a devastating impact across the world. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (the virus causing COVID-19) is known to use the receptor-binding domain (RBD) at viral surface spike (S) protein to interact with the angiotensin-converting enzyme 2 (ACE2) receptor expressed on many human cell types. The RBD-ACE2 interaction is a crucial step to mediate the host cell entry of SARS-CoV-2. Recent studies indicate that the ACE2 interaction with the SARS-CoV-2 S protein has a higher affinity than its binding with the structurally identical S protein of SARS-CoV-1, the virus causing the 2002-2004 SARS outbreak. However, the biophysical mechanism behind such binding affinity difference is unclear. This study utilizes combined single-molecule force spectroscopy and steered molecular dynamics (SMD) simulation approaches to quantify the specific interactions between SARS-CoV-2 or SARS-CoV-1 RBD and ACE2. Depending on the loading rates, the unbinding forces between SARS-CoV-2 RBD and ACE2 range from 70 to 105 pN and are 30-40% higher than those of SARS-CoV-1 RBD and ACE2 under similar loading rates. SMD results indicate that SARS-CoV-2 RBD interacts with the N-linked glycan on Asn90 of ACE2. This interaction is mostly absent in the SARS-CoV-1 RBD-ACE2 complex. During the SMD simulations, the extra RBD-N-glycan interaction contributes to a greater force and prolonged interaction lifetime. The observation is confirmed by our experimental force spectroscopy study. After removing N-linked glycans on ACE2, its mechanical binding strength with SARS-CoV-2 RBD decreases to a similar level of the SARS-CoV-1 RBD-ACE2 interaction. Together, the study uncovers the mechanism behind the difference in ACE2 binding between SARS-CoV-2 and SARS-CoV-1 and could help develop new strategies to block SARS-CoV-2 entry. |
| Databáze: | OpenAIRE |
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