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

  1. Jin Chai
  2. Yuanheng Cai
  3. Changxu Pang
  4. Liguo Wang
  5. Sean McSweeney
  6. John Shanklin
  7. Qun Liu

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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.

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  1. Version published to 10.1038/s41467-021-23533-x
  2. ScreenIT

    SciScore for 10.1101/2021.02.22.432373: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Among these particles, we produced an initial 3D model using CryoSPARC and used the model to perform 3D classifications in Relion3 for five classes with a pixel size of 2.736 Å (Fig. S2).
    CryoSPARC
    suggested: (cryoSPARC, RRID:SCR_016501)
    We used the PDB code 4WSI as a starting model and built the model for PSG and Ec18 in COOT 31 and refined the model iteratively using PHENIX.
    COOT
    suggested: (Coot, RRID:SCR_014222)
    PHENIX
    suggested: (Phenix, RRID:SCR_014224)
    The refined model was validated using Molprobity 32 and the refinement statistics is listed in Table S1.
    Molprobity
    suggested: (MolProbity, RRID:SCR_014226)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: Please consider improving the rainbow (“jet”) colormap(s) used on page 9. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

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  3. Version published to 10.1101/2021.02.22.432373v1 on bioRxiv