Backbone structure of the amantadine-blocked trans-membrane domain M2 proton channel from Influenza A virus

Biophys J. 2007 Jun 15;92(12):4335-43. doi: 10.1529/biophysj.106.090183. Epub 2007 Mar 23.

Abstract

Amantadine is known to block the M2 proton channel of the Influenza A virus. Here, we present a structure of the M2 trans-membrane domain blocked with amantadine, built using orientational constraints obtained from solid-state NMR polarization-inversion-spin-exchange-at-the-magic-angle experiments. The data indicates a kink in the monomer between two helical fragments having 20 degrees and 31 degrees tilt angles with respect to the membrane normal. This monomer structure is then used to construct a plausible model of the tetrameric amantadine-blocked M2 trans-membrane channel. The influence of amantadine binding through comparative cross polarization magic-angle spinning spectra was also observed. In addition, spectra are shown of the amantadine-resistant mutant, S31N, in the presence and absence of amantadine.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amantadine / chemistry*
  • Cell Membrane / chemistry*
  • Computer Simulation
  • Ion Channel Gating
  • Magnetic Resonance Spectroscopy
  • Models, Chemical*
  • Models, Molecular*
  • Protein Conformation
  • Protein Structure, Tertiary
  • Viral Matrix Proteins / chemistry*
  • Viral Matrix Proteins / ultrastructure*

Substances

  • M2 protein, Influenza A virus
  • Viral Matrix Proteins
  • Amantadine