Ion channel structure and function of the MERS coronavirus E protein

Area of Science:

• Structural Biology
• Virology
• Biophysics

Background:

• The Middle East respiratory syndrome (MERS) virus exhibits high mortality rates.
• The structure and function of the MERS virus envelope (E) protein, a key component in viral virulence, remain largely unknown.
• Coronavirus E proteins are known to form ion channels targeted by antiviral drugs.

Purpose of the Study:

• To determine the structure and function of the membrane-bound MERS virus E protein.
• To investigate the ion conduction properties and structural basis of the MERS E protein.

Main Methods:

• Solid-state nuclear magnetic resonance (ssNMR) spectroscopy was employed to determine the protein structure.
• Single-channel electrophysiology was used to measure ion conductance.
• Site-directed mutagenesis was performed to identify key residues for channel function.

Main Results:

• The MERS E protein forms a five-helix bundle spanning the lipid bilayer.
• MERS E conducts potassium (K+) ions with a unitary conductance of 113 picosiemens, significantly higher than SARS-CoV-2 E.
• Key residues, including phenylalanine (Phe) at positions 17 and 33, and asparagine (Asn) at position 15, are critical for ion conductance.
• Two Phe-centered ion-conduction pathways were identified, likely utilizing cation-π interactions.

Conclusions:

• The MERS E protein functions as a K+ selective ion channel with a unique structural architecture.
• The identified structural features provide a basis for the rational design of MERS-specific antiviral therapies targeting the E protein viroporin.
• Understanding the MERS E protein's ion channel activity is crucial for combating MERS-CoV infections.