Polar Networks Mediate Ion Conduction of the SARS-CoV-2 Envelope Protein

The SARS-CoV-2 E protein conducts cations across the cell membrane to cause pathogenicity to infected cells. The high-resolution structures of the E transmembrane domain (ETM) in the closed state at neutral pH and in the open state at acidic pH have been determined. However, the ion conduction mechanism remains elusive. Here, we use solid-state NMR spectroscopy to investigate the side chain structure, dynamics, and interactions of five polar residues at the N-terminal entrance of the channel and three polar residues at the C-terminal end. The chemical shifts of the N-terminal Glu8 reveal that the Glu side chain interacts with protons, Ca