7NTK

PALS1 PDZ1 domain with SARS-CoV-2_E PBM complex

Summary for 7NTK

• Entry DOI: 10.2210/pdb7ntk/pdb
• Descriptor: MAGUK p55 subfamily member 5, Envelope small membrane protein, CITRATE ANION, ... (5 entities in total)
• Functional Keywords: cell polarity, pals1, sars-cov-2_e, cell adhesion
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 8
• Total formula weight: 41662.84

Authors

Javorsky, A.,Kvansakul, M. (deposition date: 2021-03-10, release date: 2021-06-16, Last modification date: 2024-01-31)

Primary citation

Javorsky, A.,Humbert, P.O.,Kvansakul, M.
Structural basis of coronavirus E protein interactions with human PALS1 PDZ domain.
Commun Biol, 4:724-724, 2021

PubMed Abstract: SARS-CoV-2 infection leads to coronavirus disease 2019 (COVID-19), which is associated with severe and life-threatening pneumonia and respiratory failure. However, the molecular basis of these symptoms remains unclear. SARS-CoV-1 E protein interferes with control of cell polarity and cell-cell junction integrity in human epithelial cells by binding to the PALS1 PDZ domain, a key component of the Crumbs polarity complex. We show that C-terminal PDZ binding motifs of SARS-CoV-1 and SARS-CoV-2 E proteins bind the PALS1 PDZ domain with 29.6 and 22.8 μM affinity, whereas the related sequence from MERS-CoV did not bind. We then determined crystal structures of PALS1 PDZ domain bound to both SARS-CoV-1 and SARS-CoV-2 E protein PDZ binding motifs. Our findings establish the structural basis for SARS-CoV-1/2 mediated subversion of Crumbs polarity signalling and serve as a platform for the development of small molecule inhibitors to suppress SARS-CoV-1/2 mediated disruption of polarity signalling in epithelial cells.

PubMed: 34117354
DOI: 10.1038/s42003-021-02250-7

Experimental method

X-RAY DIFFRACTION (1.9 Å)