Structural Basis for SARS-CoV-2 Envelope Protein in Recognition of Human Cell Junction Protein PALS1
This article has been Reviewed by the following groups
Discuss this preprint
Start a discussion What are Sciety discussions?Listed in
- Evaluated articles (ScreenIT)
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.
Article activity feed
-
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 Sentences Resources 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). CryoSPARCsuggested: (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. COOTsuggested: (Coot, RRID:SCR_014222)PHENIXsuggested: (Phenix, RRID:SCR_014224)The refined model was validated using Molprobity 32 and the refinement statistics is listed in Table S1. Molprobitysuggested: (MolProbity, …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 Sentences Resources 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). CryoSPARCsuggested: (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. COOTsuggested: (Coot, RRID:SCR_014222)PHENIXsuggested: (Phenix, RRID:SCR_014224)The refined model was validated using Molprobity 32 and the refinement statistics is listed in Table S1. Molprobitysuggested: (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.
-
