The SARS Coronavirus E Protein Interacts with PALS1 and Alters Tight Junction Formation and Epithelial Morphogenesis

Teoh, Kim-Tat; Siu, Yu-Lam; Chan, Wing-Lim; Schlüter, Marc A.; Liu, Chia-Jen; Peiris, J. S. Malik; Bruzzone, Roberto; Margolis, Benjamin; Nal, Béatrice

Having demonstrated that E binds to the PDZ domain of PALS1 and that PALS1 is redistributed to the ERGIC and Golgi region in infected and transfected cells, we were interested in characterizing the amino acids in the E protein that are responsible for E-PALS1 interaction. We reasoned that E should contain a PDZ domain-binding motif (PBM) likely located at its carboxy-terminal tail. We found that its four carboxy-terminal amino acids (D-L-L-V) share a high degree of similarity with the carboxy-terminal PBM of CRB1 and 3 (E-R-L-I), the natural ligands of PALS1 PDZ domain. Indeed both sequences start with an acidic amino acid and end with two hydrophobic residues ([E,D]-X-Φ-Φ). Moreover, the four carboxy-terminal amino acids of E have characteristics of PDZ domain ligands (Beuming et al., 2005; Tonikian et al., 2008). Therefore, we hypothesized that the D-L-L-V carboxy-terminal peptide of E is a PDZ domain-binding motif that binds PALS1 PDZ domain.