title: The conformation of the pore region of the M2 proton channel depends on lipid bilayer environment.
abstract: The M2 protein from influenza A virus is a 97-amino-acid protein with a single transmembrane helix that forms proton-selective channels essential to virus function. The hydrophobic transmembrane domain of the M2 protein (M2TM) contains a sequence motif that mediates the formation of functional tetramers in membrane environments. A variety of structural models have previously been proposed which differ in the degree of helix tilt, with proposed tilts ranging from approximately 15 degrees to 38 degrees . An important issue for understanding the structure of M2TM is the role of peptide-lipid interactions in the stabilization of the lipid bilayer bound tetramer. Here, we labeled the N terminus of M2TM with a nitroxide and studied the tetramer reconstituted into lipid bilayers of different thicknesses using EPR spectroscopy. Analyses of spectral changes provide evidence that the lipid bilayer does influence the conformation. The structural plasticity displayed by M2TM in response to membrane composition may be indicative of functional requirements for conformational change. The various structural models for M2TM proposed to date--each defined by a different set of criteria and in a different environment--might provide snapshots of the distinct conformational states sampled by the protein.
authors.affiliation: Department of Chemistry, Swarthmore College, Swarthmore, PA 19081, USA.
authors.forename: Krisna C
authors.initials: KC
authors.lastname: Duong-Ly
authors.forename: Vikas
authors.initials: V
authors.lastname: Nanda
authors.forename: William F
authors.initials: WF
authors.lastname: Degrado
authors.forename: Kathleen P
authors.initials: KP
authors.lastname: Howard
mesh_terms: D004578:Electron Spin Resonance Spectroscopy; D007473:Ion Channels / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry*; D008958:Models, Molecular; D011487:Protein Conformation; D014763:Viral Matrix Proteins / Q000737:chemistry*; D000086082:Viroporin Proteins
chemical_list: D007473:Ion Channels; D008051:Lipid Bilayers; D014763:Viral Matrix Proteins; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins
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