pH-induced conformational change of the influenza M2 protein C-terminal domain

Biochemistry. 2008 Sep 23;47(38):9934-6. doi: 10.1021/bi801315m. Epub 2008 Aug 29.


The M2 protein from influenza A is a pH-activated proton channel that plays an essential role in the viral life cycle and serves as a drug target. Using spin labeling EPR spectroscopy, we studied a 38-residue M2 peptide spanning the transmembrane region and its C-terminal extension. We obtained residue-specific environmental parameters under both high- and low-pH conditions for nine consecutive C-terminal sites. The region forms a membrane surface helix at both high and low pH, although the arrangement of the monomers within the tetramer changes with pH. Both electrophysiology and EPR data point to a critical role for residue Lys 49.

Publication types

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

MeSH terms

  • Animals
  • Electron Spin Resonance Spectroscopy
  • Hydrogen-Ion Concentration
  • Influenza A virus / chemistry*
  • Lysine / chemistry
  • Protein Conformation
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Viral Matrix Proteins / chemistry*
  • Xenopus laevis


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