Related Experiment Videos
The transmembrane domain of influenza A M2 protein forms amantadine-sensitive proton channels in planar lipid
1Department of Biochemistry, University of Edinburgh, U.K.
Abstract:
In a direct test of the hypothesis that the M2 coat protein of influenza A can function as a proton translocator, we incorporated a synthetic peptide containing its putative transmembrane domain into voltage-clamped planar lipid bilayers. We observed single proton-selective ion channels with a conductance of approximately 10 pS at a pH of 2.3, consistent with the association of several monomers around a central water-filled pore. The channels were reversibly blocked by the anti-influenza drug amantadine. These experiments imply a central role for M2 protein in virus replication and assembly and may explain the mechanism of action of amantadine. Analogous proteins may have a similar function in other viruses, and these may be susceptible to similar antiviral agents.
Insights
The M2 protein of influenza A acts as a proton channel, forming pores blocked by amantadine. This finding clarifies virus replication and amantadine
Area of Science:
- Virology
- Biophysics
- Membrane Protein Function
Background:
- The M2 protein is a key component of the influenza A virus.
- Its role in proton translocation has been hypothesized but not directly demonstrated.
- Understanding M2 function is crucial for developing antiviral strategies.
Purpose of the Study:
- To directly test the hypothesis that the M2 coat protein of influenza A functions as a proton translocator.
- To investigate the mechanism of action of the anti-influenza drug amantadine.
Main Methods:
- Incorporation of a synthetic peptide representing the M2 protein's transmembrane domain into voltage-clamped planar lipid bilayers.
- Electrophysiological recordings to observe ion channel activity and selectivity.
- Testing the effect of amantadine on channel function.
Main Results:
- Observation of single proton-selective ion channels with a conductance of approximately 10 pS at pH 2.3.
- Evidence suggests the association of several M2 monomers forming a central pore.
- Reversible blockage of these channels by amantadine.
Conclusions:
- The M2 protein of influenza A directly functions as a proton translocator.
- This proton channel activity is essential for virus replication and assembly.
- Amantadine's antiviral mechanism involves blocking the M2 proton channel.