Structural Basis for SARS-CoV-2 Envelope Protein in Recognition of Human Cell Junction Protein PALS1

Abstract The COVID-19 pandemic caused by the SARS-CoV-2 virus has created a global health and economic emergency. SARS-CoV-2 viruses hijack human proteins to promote their spread and virulence including the interactions involving the viral envelope (E) protein and human proteins. To understand the s...

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Bibliographic Details
Published in:bioRxiv 2021-02
Main Authors: Chai, Jin, Cai, Yuanheng, Pang, Changxu, Wang, Liguo, Mcsweeney, Sean, Shanklin, John, Liu, Qun
Format: Article
Language:English
Subjects:
Cell junctions
COVID-19
Electron microscopy
Epithelial cells
Hydrophobicity
Pandemics
Protein C
Protein structure
Proteins
Public health
Severe acute respiratory syndrome coronavirus 2
Viral envelope proteins
Virulence
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Summary:Abstract The COVID-19 pandemic caused by the SARS-CoV-2 virus has created a global health and economic emergency. SARS-CoV-2 viruses hijack human proteins to promote their spread and virulence including the interactions involving the viral envelope (E) protein and human proteins. To understand the structural basis for SARS-CoV-2 viral-host recognition, we used cryo-electron microscopy to determine a structure for the human cell junction protein PALS1 and SARS-CoV-2 E protein complex. The structure shows that the E protein C-terminal DLLV motif recognizes a pocket formed exclusively by hydrophobic residues from the PDZ and SH3 domains in PALS1. Our structural analysis provides an explanation for the observation that the viral E protein recruits PALS1 from lung epithelial cell junctions resulting in vascular leakage, lung damage, viral spread, and virulence. In addition, our structure provides novel targets for peptide- and small-molecule inhibitors that could block the PALS1-E interactions to reduce the E-mediated damage to vascular structures. Competing Interest Statement The authors have declared no competing interest.
DOI:10.1101/2021.02.22.432373