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Updated: Jun 24, 2026

Site Directed Spin Labeling and EPR Spectroscopic Studies of Pentameric Ligand-Gated Ion Channels
11:19

Site Directed Spin Labeling and EPR Spectroscopic Studies of Pentameric Ligand-Gated Ion Channels

Published on: July 4, 2016

pH-driven helix rotations in the influenza M2 H+ channel: a potential gating mechanism

Hadas Leonov1, Isaiah T Arkin

  • 1Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Edmund J. Safra Campus Givat-Ram, 91904, Jerusalem, Israel. hleonov@cc.huji.ac.il

European Biophysics Journal : EBJ
|April 4, 2009
PubMed

Insights

Influenza A M2 H(+) channel gating involves histidine protonation and helix rotation. Molecular dynamics simulations confirm that helix rotation leads to channel closure and increased histidine solvation.

Area of Science:

  • Biophysics
  • Structural Biology
  • Computational Biology

Background:

  • The influenza A M2 H(+) channel is a drug target due to its role in viral uncoating.
  • Its small size and pH-gated mechanism, controlled by histidine residues, make it ideal for biophysical studies.
  • Previous FTIR studies suggested helix rotation during pH activation.

Purpose of the Study:

  • To investigate the molecular mechanism of M2 H(+) channel gating using molecular dynamics (MD) simulations.
  • To compare the stability, water interactions, and histidine hydration in open and closed channel states.
  • To elucidate the role of histidine protonation in channel gating.

Main Methods:

  • Molecular dynamics simulations of the M2 H(+) channel X-ray structure.
  • Simulations included charged histidines (open state) and neutral histidines (closed state).
  • Analysis of channel stability, convergence, water interaction, and histidine hydration.

Main Results:

  • Both open (charged histidines) and closed (neutral histidines) forms of the M2 channel are stable during MD simulations.
  • Helix rotation about directors was confirmed to lead to channel closure.
  • Histidine protonation is linked to increased solvation and is proposed as a key gating event.

Conclusions:

  • The study supports a model where helix rotation drives M2 channel gating.
  • Protonation of histidine residues, leading to increased solvation, is crucial for channel activation.
  • MD simulations provide valuable insights into the gating mechanism of the influenza A M2 H(+) channel.

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