Publication date: Jul 11, 2025
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. Mutation of Phe abolished K conductance, whereas mutations of Phe and Asn suppressed most channel activity. These results indicate that MERS E contains two Phe-centered ion-conduction apparatuses, which likely permeate ions through cation-π interactions, providing the structural basis for developing antiviral drugs to inhibit this pathogenic viroporin.
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Semantics
| Type | Source | Name |
|---|---|---|
| disease | IDO | virulence |
| disease | MESH | Middle East respiratory syndrome |
| drug | DRUGBANK | L-Phenylalanine |
| drug | DRUGBANK | L-Asparagine |
| drug | DRUGBANK | Potassium |