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 has previously been shown to interfere with the control of cell polarity in human epithelial cells by binding to the PDZ domain of PALS1, a key component of the Crumbs polarity complex. We now show that the C-terminal PDZ binding motifs of SARS-CoV-1 and SARS-CoV-2 bind the PALS1 PDZ domain with 28.4 and 22.8 mM affinity, whereas the related sequence from MERS-CoV did not show any binding. We then determined the 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 disrupt SARS-CoV-1/2 mediated disruption of polarity signalling in epithelial cells.