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A functionally defined model for the M2 proton channel of influenza A virus suggests a mechanism for its ion

L H Pinto1, G R Dieckmann, C S Gandhi

  • 1Department of Neurobiology and Physiology, Northwestern University, Evanston, IL 60208-3500, USA.

Proceedings of the National Academy of Sciences of the United States of America
|October 23, 1997
PubMed

Insights

Influenza A virus M2 protein forms proton channels crucial for viral function. Researchers mapped mutations to understand channel structure and amantadine drug resistance, revealing insights into proton selectivity.

Area of Science:

  • Virology
  • Structural Biology
  • Membrane Biophysics

Background:

  • The M2 protein of influenza A virus forms proton channels essential for viral replication.
  • These proton channels are a key target for antiviral drugs like amantadine.
  • Understanding the M2 channel's structure is vital for developing new antiviral therapies.

Purpose of the Study:

  • To investigate the structural basis of proton selectivity in the influenza A virus M2 channel.
  • To elucidate the relationship between M2 protein mutations, channel function, and amantadine resistance.
  • To develop a three-dimensional model of the M2 channel's transmembrane segment.

Main Methods:

  • Utilized cysteine scanning mutagenesis to create a series of M2 protein mutants.
  • Expressed M2 mutants in Xenopus laevis oocytes for functional analysis.
  • Measured reversal potential, ion currents, and amantadine resistance of M2 channel mutants.
  • Applied Fourier analysis to determine the periodicity of the M2 protein structure.

Main Results:

  • Identified mutations affecting M2 channel ion transport and amantadine sensitivity.
  • Fourier analysis indicated a structural periodicity consistent with a four-stranded coiled coil or helical bundle.
  • The study provides experimental data supporting a specific oligomeric state for the M2 channel.

Conclusions:

  • The M2 protein likely forms a four-stranded helical bundle in the viral membrane.
  • This structural arrangement provides a framework for understanding the M2 channel's proton selectivity mechanism.
  • Insights gained can inform the design of novel influenza antivirals targeting the M2 channel.

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