Solution structure and functional analysis of the influenza B proton channel

Area of Science:

• Virology
• Structural Biology
• Biochemistry

Background:

• Influenza B virus utilizes the BM2 protein, an integral membrane protein, to form a pH-activated proton channel.
• Understanding the structure of BM2 is crucial for elucidating its function in viral processes.

Purpose of the Study:

• To determine the solution structures of the membrane-embedded channel domain and the cytoplasmic domain of the BM2 protein.
• To investigate the mechanism of proton conductance and identify key residues involved in ion transport.
• To explore the interaction between the BM2 cytoplasmic domain and the M1 matrix protein.

Main Methods:

• Solution structure determination using biophysical techniques.
• Site-directed mutagenesis to probe protein function.
• Proton flux assays to measure ion channel activity.

Main Results:

• The BM2 channel domain forms a left-handed coiled-coil tetramer, creating a polar pore for ion conduction.
• Specific residues were identified as critical for proton relay, suggesting a conductance mechanism.
• The BM2 cytoplasmic domain also forms a coiled-coil tetramer with a bipolar charge distribution.
• A specific interaction between the negatively charged region of BM2 and the M1 matrix protein was observed.

Conclusions:

• The BM2 protein functions as a pH-activated proton channel through a tetrameric coiled-coil structure.
• BM2 plays a dual role, facilitating ion transport and recruiting M1 matrix proteins to the cell surface during virus budding.
• This dual functionality highlights BM2 as an unusual viral membrane protein with significant implications for influenza virus assembly and infection.