Structural basis for SARS-CoV-2 envelope protein recognition of human cell junction protein PALS1.

Nature Communications
Jin ChaiQun Liu

Abstract

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.

References

Jul 21, 2004·Journal of Computational Chemistry·Eric F PettersenThomas E Ferrin
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Paul D AdamsPeter H Zwart
Aug 5, 2011·Assay and Drug Development Technologies·Moran Jerabek-WillemsenStefan Duhr
Nov 12, 2014·Proceedings of the National Academy of Sciences of the United States of America·Youjun LiMingjie Zhang
Nov 26, 2015·Journal of Structural Biology·Kai Zhang
Jan 23, 2016·Pathogens·Claire D James, Sally Roberts
Jul 25, 2016·Diseases·Yvonne Xinyi LimDing Xiang Liu
Oct 27, 2017·Protein Science : a Publication of the Protein Society·Christopher J WilliamsDavid C Richardson
May 28, 2019·Virology Journal·Dewald Schoeman, Burtram C Fielding
Jul 25, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Luis H Gutiérrez-González, Teresa Santos-Mendoza
Nov 16, 2019·Protein Science : a Publication of the Protein Society·Ana CasañalPaul Emsley
Mar 21, 2020·Lancet·Puja MehtaUNKNOWN HLH Across Speciality Collaboration, UK
Apr 22, 2020·Advanced Therapeutics·Nikolaj R ChristensenKristian Strømgaard
Jul 10, 2020·Current Opinion in Structural Biology·J L VilasCos Sorzano
Jul 23, 2020·IUCrJ·Donal M McSweeneyQun Liu
Nov 13, 2020·Nature Structural & Molecular Biology·Venkata S MandalaMei Hong
Dec 16, 2020·Gene Reports·M Shaminur RahmanM Anwar Hossain
Feb 3, 2021·International Journal of Molecular Sciences·Nicholas A Wong, Milton H Saier
Apr 18, 2021·The FEBS Journal·Célia Caillet-SaguyNicolas Wolff

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Citations

Oct 29, 2021·Biochemical Society Transactions·Gabriel C Lander, Robert M Glaeser

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