| Autor: |
Chai J; Biology Department, Brookhaven National Laboratory, Upton, NY, USA., Cai Y; Biochemistry and Cell Biology Department, Stony Brook University, Stony Brook, NY, USA., Pang C; Biology Department, Brookhaven National Laboratory, Upton, NY, USA., Wang L; Laboratory for Biomolecular Structure, Brookhaven National Laboratory, Upton, NY, USA., McSweeney S; NSLS-II, Brookhaven National Laboratory, Upton, NY, USA., Shanklin J; Biology Department, Brookhaven National Laboratory, Upton, NY, USA.; Biochemistry and Cell Biology Department, Stony Brook University, Stony Brook, NY, USA., Liu Q; Biology Department, Brookhaven National Laboratory, Upton, NY, USA. qunliu@bnl.gov.; NSLS-II, Brookhaven National Laboratory, Upton, NY, USA. qunliu@bnl.gov. |
| Abstrakt: |
The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has created global health and economic emergencies. SARS-CoV-2 viruses promote their own spread and virulence by hijacking human proteins, which occurs through viral protein recognition of human targets. To understand the structural basis for SARS-CoV-2 viral-host protein recognition, here we use cryo-electron microscopy (cryo-EM) to determine a complex structure of the human cell junction protein PALS1 and SARS-CoV-2 viral envelope (E) protein. Our reported structure shows that the E protein C-terminal DLLV motif recognizes a pocket formed exclusively by hydrophobic residues from the PDZ and SH3 domains of PALS1. Our structural analysis provides an explanation for the observation that the viral E protein recruits PALS1 from lung epithelial cell junctions. In addition, our structure provides novel targets for peptide- and small-molecule inhibitors that could block the PALS1-E interactions to reduce E-mediated virulence. |
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