7M4R

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

Summary for 7M4R

• Entry DOI: 10.2210/pdb7m4r/pdb
• EMDB information: 23665
• Descriptor: MAGUK p55 subfamily member 5, Envelope small membrane protein (2 entities in total)
• Functional Keywords: sars-cov-2 envelope protein, pdz-binding motif, complex, pathogen-host interaction, cell adhesion-viral protein complex, cell adhesion/viral protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 91623.40

Authors

Liu, Q.,Chai, J. (deposition date: 2021-03-22, release date: 2021-03-31, Last modification date: 2025-06-04)

Primary citation

Chai, J.,Cai, Y.,Pang, C.,Wang, L.,McSweeney, S.,Shanklin, J.,Liu, Q.
Structural basis for SARS-CoV-2 envelope protein recognition of human cell junction protein PALS1.
Nat Commun, 12:3433-3433, 2021

PubMed 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.

PubMed: 34103506
DOI: 10.1038/s41467-021-23533-x

Experimental method

ELECTRON MICROSCOPY (3.65 Å)