Initial structural and dynamic characterization of the M2 protein transmembrane and amphipathic helices in lipid bilayers

Changlin Tian, Philip Fei Gao, Lawrence H. Pinto, Robert A. Lamb, Timothy A. Cross*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

119 Scopus citations

Abstract

Amphipathic helices in membrane proteins that interact with the hydrophobic/hydrophilic interface of the lipid bilayer have been difficult to structurally characterize. Here, the backbone structure and orientation of an amphipathic helix in the full-length M2 protein from influenza A virus has been characterized. The protein has been studied in hydrated DMPC/DMPG lipid bilayers above the gel to liquid-crystalline phase transition temperature by solid-state NMR spectroscopy. Characteristic PISA (Polar Index Slant Angle) wheels reflecting helical wheels have been observed in uniformly aligned bilayer preparations of both uniformly 15N labeled and amino acid specific labeled M2 samples. Hydrogen/deuterium exchange studies have shown the very slow exchange of some residues in the amphipathic helix and more rapid exchange for the transmembrane helix. These latter results clearly suggest the presence of an aqueous pore. A variation in exchange rate about the transmembrane helical axis provides additional support for this claim and suggests that motions occur about the helical axes in this tetramer to expose the entire backbone to the pore.

Original languageEnglish (US)
Pages (from-to)2597-2605
Number of pages9
JournalProtein Science
Volume12
Issue number11
DOIs
StatePublished - Nov 2003

Keywords

  • Amphipathic helices
  • Hydrogen-deuterium exchange
  • Influenza A
  • M2 proton channel
  • Membrane protein structure
  • PISA wheel
  • PISEMA
  • Solid-state NMR

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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