Abstact

Coronavirus envelope (E) proteins form drug-targeted ion channels that cause virulence to infected cells. The Middle East respiratory syndrome (MERS) virus has high mortality rates, but its E structure and function are unknown. We report the single-channel conductance and structure of membrane-bound MERS E protein. MERS E conducts K(+) ions with a unitary conductance of 113 picosiemens, fivefold larger than the conductance of severe acute respiratory syndrome coronavirus 2 E. Solid-state nuclear magnetic resonance data indicate that the MERS E transmembrane domain forms a five-helix bundle that spans the lipid bilayer. The amino-terminal helical interface features multiple interacting phenylalanine (Phe) residues and an asparagine (Asn), whereas the carboxyl-terminal channel pore contains Phe(33). Mutation of Phe(17) abolished K(+) conductance, whereas mutations of Phe(33) and Asn(15) suppressed most channel activity. These results indicate that MERS E contains two Phe-centered ion-conduction apparatuses, which likely permeate ions through cation-pi interactions, providing the structural basis for developing antiviral drugs to inhibit this pathogenic viroporin.