Experimentally based orientational refinement of membrane protein models: A structure for the influenza A M2 H+ channel

Andreas Kukol, Paul D. Adams, Luke M. Rice, Axel T. Brunger, Isaiah T. Arkin

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133 Scopus citations


The 97-residue M2 protein from Influenza A virus forms H+-selective ion channels which can be attributed solely to the homo-tetrameric α-helical transmembrane domain. Site-directed infrared dichroism spectra were obtained for the transmembrane domain of M2, reconstituted in lipid vesicles. Data analysis yielded the helix tilt angle β = 31.6 (± 6.2)°and the rotational pitch angle about the helix axis for residue Ala29 ω(Ala29) = -59.8 (± 9.9)°, whereby ω is defined as zero for a residue located in the direction of the helix tilt. A structure was obtained from an exhaustive molecular dynamics global search protocol in which the orientational data are utilised directly as an unbiased refinement energy term. Orientational refinement not only allowed selection of a unique structure but could also be shown to increase the convergence towards that structure during the molecular dynamics procedure. Encouragingly, the structure obtained is highly consistent with all available mutagenesis and conductivity data and offers a direct chemical insight that relates the altered functionality of the channel to its structure.

Original languageAmerican English
Pages (from-to)951-962
Number of pages12
JournalJournal of Molecular Biology
Issue number3
StatePublished - 26 Feb 1999
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by a grant from the Wellcome Trust. L.M.R. is supported by a predoctoral fellowship from the Howard Hughes Medical Institute.


  • Influenza
  • Infrared spectroscopy
  • Ion channel
  • M2-protein
  • Molecular dynamics


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