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Structural Basis for SARS-CoV-2 Envelope Protein in Recognition of Human Cell Junction Protein PALS1
Jin Chai; Yuanheng Cai; Changxu Pang; Liguo Wang; Sean McSweeney; John Shanklin; Qun Liu.
Afiliação
  • Jin Chai; Brookhaven National Laboratory
  • Yuanheng Cai; Stony Brook University
  • Changxu Pang; Brookhaven National Laboratory
  • Liguo Wang; Brookhaven National Laboratory
  • Sean McSweeney; Brookhaven National Laboratory
  • John Shanklin; Brookhaven National Laboratory
  • Qun Liu; Brookhaven National Laboratory
Preprint em En | PREPRINT-BIORXIV | ID: ppbiorxiv-432373
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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.
Licença
cc_by_nc
Texto completo: 1 Coleções: 09-preprints Base de dados: PREPRINT-BIORXIV Tipo de estudo: Observational_studies / Prognostic_studies Idioma: En Ano de publicação: 2021 Tipo de documento: Preprint
Texto completo: 1 Coleções: 09-preprints Base de dados: PREPRINT-BIORXIV Tipo de estudo: Observational_studies / Prognostic_studies Idioma: En Ano de publicação: 2021 Tipo de documento: Preprint