PH-driven helix rotations in the inXuenza M2 H+ channel: A potential gating mechanism

Hadas Leonov, Isaiah T. Arkin

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


The pH activated M2 H+ channel from inXuenza A has been a subject of numerous studies due to following: (1) It serves as a target for the aminoadamantane drugs that block its channel activity. (2) M2's small size makes it amenable to biophysical scrutiny. (3) A single histidine residue is thought to control the pH gating of the channel. Recent FTIR analysis proposed that the helices of the channel rotate about their directors during pH activation. Herein, we report on molecular dynamics simulations of the X-ray structure of the protein with three charged histidine residues, representing the open form of the protein and two rotated forms with neutral histidines, representing its closed form. We compare the channel stability, convergence, interaction with water and hydration of the histidine residues that have been implicated in channel gating. Taken together, we show that both forms of the protein are stable during the course of the MD simulation and that indeed a rotation of the helices leads to channel closure. Finally, we propose a mechanism for channel gating that involves protonation of the histidine residues that necessities their increased solvation.

Original languageAmerican English
Pages (from-to)1043-1049
Number of pages7
JournalEuropean Biophysics Journal
Issue number7
StatePublished - Jun 2010

Bibliographical note

Funding Information:
Acknowledgments This work was supported in part by grants from the Israeli science foundation (784/01,1249/05,1581/08) to ITA. ITA is the Arthur Lejwa Professor of Structural Biochemistry at the Hebrew University of Jerusalem. Molecular Wgures were generated by VMD (Humphrey et al. 1996).


  • InXuenza
  • Ion channel
  • M2 channel
  • Molecular dynamics
  • Protein structure


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