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bioRxiv · 10.1101/2021.02.22.432373

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

Chai, J.·Cai, Y.·Pang, C.·Wang, L.·McSweeney, S.·Shanklin, J.·Liu, Q.
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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.

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Chai, J., Cai, Y., Pang, C., Wang, L., McSweeney, S., Shanklin, J., Liu, Q.. 2021-02-23. Structural Basis for SARS-CoV-2 Envelope Protein in Recognition of Human Cell Junction Protein PALS1. https://doi.org/10.1101/2021.02.22.432373

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